Influence of first trimester biochemistry methodology on detection rate in screening for trisomy 21.

OBJECTIVES: The purpose of the study was to compare detection rates (DR) of FMF-certified and non-certified biochemical tests (BC) in trisomy 21 screening at 11-13 + 6 weeks. MATERIAL AND METHODS: In 2267 singleton pregnancies FMF-certified doctors measured crown to rump length (CRL) and nuchal translucency (NT). Serum samples were tested for free ß-hCG and the PAPP-A using 2 analysers (Delfia - Perkin Elmer and Immulite 2000 - DPC), the results were expressed in MoM values and used for computer calculation of the risk for trisomy 21. The cut-off value for the high trisomy 21 risk was 1:300. RESULTS: Comparison of free ß-hCG MoMs by DPC and Delfia demonstrated statistically significant differences in normal, and trisomy 21 fetuses respectively. Similarly, statistically significant differences were noted for PAPP-A MoMs. The above differences in MoMs resulted in altered sensitivity in screening for aneuploidy. The application of the FMF-certified method ensures a markedly higher DR = 74%, compared to non-certified tests (64%), both at 5% FPR. The ROC analysis was performed in order to assess the efficacy of both tests. Results of trisomy 21 BC + NT risk scales using the Delfia and DPC methods are highly significant (p < 0.0001), which means that their discrimination ability is > 90%. The difference between results obtained using the Delfia and DPC methods is AUC = 0.0150 and is statistically significant (Z = 2.4728, p = 0.0134). CONCLUSIONS: The use of FMF-certified first trimester biochemistry analysers improves DR for trisomy 21. The use of non-certified analysers causes reduction of DR and an increase of invasive procedure rate.

Screening for trisomy 21 based on maternal age, nuchal translucency measurement, first trimester biochemistry and quantitative and qualitative assessment of the flow in the DV - the assessment of efficacy.

OBJECTIVES: The aim of the study was to compare effects of addition of two methods of ductus venosus (DV) flow assessment: qualitative - the assessment of shape of the A-wave (positive or negative), and quantitative - based on the pulsatility index for veins (DVPI) to the basic screening for trisomy 21 at 11 to 13 + 6 weeks of pregnancy. MATERIAL AND METHODS: The ultrasound examination was performed in 8230 fetuses in singleton pregnancies at 11- -13 + 6 wks, as a part of a routine screening for chromosomal defects. In DV A-wave was assessed and DVPI was calculated. After the scan blood sample was taken for first trimester biochemistry (BC). Risk for chromosomal defects was calculated and high-risk patients were offered an invasive test for karyotyping. RESULTS: Basic screening with following combination of markers: MA, NT and BC provided lowest detection rate (DR) 87.50% for FPR = 6.94%. After adding qualitative DV A-wave assessment DR increased to 88.75% for FPR = 5.65%. The best DR = 93.75% for FPR = 5.55% was achieved when quantitative DVPI was added. The application of the Receiver Operating Curves curve confirmed validity of the addition of DV flow assessment to the screening model. The highest diagnostic power of the test was achieved when DVPI was added, with the ROC AUC of 0.974. CONCLUSIONS: The assessment of DV flow performed at 11-13 + 6 weeks increases DR for trisomy 21 and reduces FPR. The screening model based on the quantitative DV flow analysis (DVPI) gives better results compared to the qualitative flow assessment.

Nasal bone in screening for T21 at 11-13 + 6 weeks of gestation - a multicenter study.

OBJECTIVES: Trisomy 21 is one of the most common chromosomal defects diagnosed prenatally. Screening for Down syndrome is based on maternal age, measurement of crown-rump length, nuchal translucency and fetal heart rate, together with free ß-hCG and PAPP-A at 11 to 13 + 6 weeks. Introduction of additional ultrasound marker of trisomy 21 (evaluation of the nasal bone) may result in increased DR and decreased invasive diagnostic testing rates (FPR). MATERIAL AND METHODS: Ultrasound scan with NB evaluation was performed in 5814 fetuses during routine screening for chromosomal defects at 11 to 13 + 6 weeks of gestation. DR and FPR coefficients were calculated for 4 levels of risk as cut-off points for screening model 1, based on MA, NT, and first trimester biochemistry, as well as for screening model 2, based on MA, NT, first trimester biochemistry and NB. RESULTS: There were 5708 normal cases, 71 cases of trisomy 21 and 35 cases of other chromosomal defects. NB was absent in 46 (64.8%) cases and present in 25 (35.3%) cases of trisomy 21, comparing to present NB in 5463 (95.7%) and absent in 245 (4.3%) of normal cases. CONCLUSIONS: First-semester screening with additional NB assessment significantly increases the detection rate for trisomy 21 and decreases the rate of false-positive results. Adding NB evaluation at the risk level of 1:50 causes only a small increase in detection rate. Invasive procedures should be performed in that group regardless NB assessment.

The evolution of fetal presentation during pregnancy: a retrospective, descriptive cross-sectional study.

We investigated changes in the frequencies of four primary types of singleton fetal lie/presentation for each gestational week from 18 to 39 weeks in a retrospective, cross-sectional study which analyzed ultrasound examination records of fetal positions, in the outpatient prenatal diagnosis clinics in two cities in Poland. We calculated the prevalence and 95% confidence intervals for each type of lie/presentation. We then identified the gestational age after which no statistically significant changes in terms of prevalence were observed, by comparing the results at each week with the prevalence of cephalic presentation at 39(+0) weeks, used as reference. A total of 18 019 ultrasound examinations were used. From 22 to 36 weeks of gestation, the prevalence of cephalic presentation increased from 47% (45-50%) to 94% (91-96%), before and after which times plateaus were noted. Spontaneous change from breech to cephalic is unlikely to occur after 36 weeks of gestation.

Does prior knowledge of maternal age affect judgment of operators measuring nuchal translucency?

OBJECTIVES: To test the hypothesis that, in real life standard clinical practice, knowledge of maternal age (MA) by operators measuring nuchal translucency (NT) for screening of aneuploidy may influence their judgment, resulting in a tendency to over-measurement in older women. MATERIAL AND METHODS: We retrospectively analyzed the correlation between MA and NT MoMs in data from a group of operators from several clinical practices, with different levels of experience. RESULTS: We assessed 66,918 measurements by 41 operators. There was no association between NT and MA in all the measurements analyzed together In 3 experienced operators (N > 1900), there was a significant association between the variables, although all were negative and its effect size was very small (0.004, 0.006 and 0.01). However one of the less experienced operators (N = 47) had a statistically significant (p = 0.0002) and strong (R2 = 0.2634) association. We tested the hypothesis that this bias could occur in less experienced operators but time/experience would correct it. We did the same analyses for each set of 50 tests, sorted by date, for each operator up to the 7th set. No significant progression was identified in association with increase in experience. CONCLUSIONS: Our data does not support the hypothesis that operators might be biased towards over-measuring NT in older women.

[Agenesis of the ductus venosus--an irrelevant anomaly or a severe clinical problem?]. / Agenezja przewodu zylnego--niegrozna nieprawidlowosc rozwojowa czy powazny problem kliniczny?

BACKGROUND: Ductus venosus is the fetal blood vessel connecting the abdominal portion of the umbilical vein with the inferior vena cava. Numerous studies have confirmed the important role of this vessel in fetal circulation. There are, however cases when finding the ductus venosus during an ultrasound examination is impossible. OBJECTIVE: The objective of the study was to assess the fate of fetuses with known ductus venosus agenesis and its severity in fetal life. MATERIAL AND METHODS: 17 fetuses from singleton pregnancies with agenesis of the ductus venosus were observed and followed up. RESULTS: A total of 3 intrauterine deaths, preceded by fetal hydrops and signs of heart failure, were observed in the study group. One newborn required cardiac care after birth. In the majority of cases with ductus venosus agenesis, where no accompanying developmental anomalies were found, prognosis for the fetus and the newborn was good. CONCLUSIONS: Cases of ductus venosus agenesis should be directed to and followed up in referral centers, where adequate diagnostic and therapeutic procedures can be undertaken.

[Frontomaxillary facial angle measurement at 11+0 to 13+6 weeks' gestation. Application in every day prenatal diagnosis of trisomy 21]. / Pomiar kata twarzowo-szczekowego u plodów pomiedzy 11+0 a 13+6. tygodniem ciazy. Zastosowanie w diagnostyce prenatalnej trisomii 21.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of prenatal screening for trisomy 21 with the use of the FMF angle measurement, depending on the disease risk group. MATERIAL AND METHODS: The study included 2,026 single pregnancy fetuses, examined in years 2009-2011. The crown-rump length, nuchal translucency and frontomaxillary facial angle were measured for each of the fetuses according to the Fetal Medicine Foundation guidelines. All ultrasound exams were performed using trans-abdominal probes paired with Voluson 730 Expert and Expert E8 systems. All physicians conducting the exams were FMF-certified professionals. Maternal age at the time of the study was also reported. In 1621 pregnant women serum concentration of PAPP-A was determined using Delfia Express system (Perkin Elmer). Astraia software was used to assess fetal risk of trisomy 21. The final analysis included 791 fetuses which were followed up for the occurrence of trisomy 21. Data were analyzed using PQStat package ver 1.4.2.324. Highly significant likelihood was set at p < 0.01 and significant likelihood at p < 0.05. RESULTS: Average maternal age was 31.42 years (median: 32 in a range from 27 to 45). Average FMF angle was 76.24 degrees (median: 75 degrees in a range from 69 to 04). Average CRL measurements was 63.70 mm (median: 64.10 mm in a range from 45 to 84). Average NT measurement was 1.91 mm (median: 1.6 mm in a range from 0.50 to 9.3). There was no significant (p > 0.05) correlation between maternal age and FMF. Highly significant (p < 0.01) negative correlation between the CRL and the FMF angle was found. There were 41 fetuses with trisomy 21 (Down syndrome) in the study group. In the normal karyotype group, the FMF angle was highly significantly lower (p < 0.0001) than in the trisomy 21 group. 95th percentile of the each of four separated CRL ranges was calculated. Detection rate and false positive rate for each of four different risk levels were estimated. They were used as cutoff points for two models of first trimester screening compared: Model 1, including maternal age, NT measurement and PAPP-A test, and Model 2, including maternal age, NT measurement, PAPP-A test and Frontomaxillary facial angle measurement. CONCLUSIONS: 1. Detection rate (DR) of the Down syndrome increases after the introduction of FMF angle measurement as an additional component of screening including maternal age, NT measurement and PAPP-A test. 2. Introduction of the FMF angle as an independent marker for fetal trisomy 21 risk requires further research on large populations.

Risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic: Results of a web-based multinational cross-sectional study.

OBJECTIVE: To assess risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic using Mind-COVID, a prospective cross-sectional study that compares outcomes in middle-income economies and high-income economies. METHODS: A total of 7102 pregnant women from 12 high-income economies and nine middle-income economies were included. The web-based survey used two standardized instruments, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). RESULT: Pregnant women in high-income economies reported higher PHQ-9 (0.18 standard deviation [SD], P < 0.001) and GAD-7 (0.08 SD, P = 0.005) scores than those living in middle-income economies. Multivariate regression analysis showed that increasing PHQ-9 and GAD-7 scales were associated with mental health problems during pregnancy and the need for psychiatric treatment before pregnancy. PHQ-9 was associated with a feeling of burden related to restrictions in social distancing, and access to leisure activities. GAD-7 scores were associated with a pregnancy-related complication, fear of adverse outcomes in children related to COVID-19, and feeling of burden related to finances. CONCLUSIONS: According to this study, the imposed public health measures and hospital restrictions have left pregnant women more vulnerable during these difficult times. Adequate partner and family support during pregnancy and childbirth can be one of the most important protective factors against anxiety and depression, regardless of national economic status.

"The Killer Placenta" - a threat to the lives of young women giving birth by cesarean section.

OBJECTIVES: It is necessary to create a universal algorithm for the management of placenta accreta spectrum in order to minimize morbidity and mortality in young patients giving birth by caesarean section. MATERIAL AND METHODS: This was a retrospective study of seven women before the age of 30 selected out of larger group of 40 pregnant patients. The patients were hospitalized in the Clinical Department of Perinatology, Gynecology and Obstetrics in Ruda Slaska, which is a 3rd level reference department. The inclusion criterion was the suspicion of placent accreta spectrum, based on clinical condition, ultrasound examination and magnetic resonance imaging. RESULTS: A patient with a diagnosed placenta accreta spectrum should be provided with a highly specialized 3rd level referential center by an experienced multidisciplinary team of specialists. There should be free access to the blood bank, adult intensive care unit and neonatal intensive care unit. According to the results of this study, the recommended time of cesarean section is 34 + 0 - 36 + 6 weeks of pregnancy. Hysterectomy after the cesarean section is a method of choice for a placenta increta or percreta. It is the most difficult surgery in obstetrics, with a high risk of intraoperative complications. Damage to the urinary system is the most common complication of perinatal hysterectomy. Preoperative placement of ureteral catheters reduces the risk of intraoperative damage. CONCLUSIONS: It is necessary to plan individual procedure for women who has low-lying or previa placenta, and who has history of prior cesarean section - in this group the risk of placenta accreta spectrum is higher.

The role of individual blood flow parameters through ductus venosus in the first and second trimesters of pregnancy in predicting the condition of the fetus and newborn.

OBJECTIVES: To predict fetal and neonatal outcome during pregnancy based on detailed analysis of ductus venosus blood flow velocities in first and second-trimester fetuses. MATERIAL AND METHODS: A retrospective analysis was made in 680 patients with single pregnancies in years 2015 and 2016. The following ductus venosus blood flow velocities in first and second-trimester were analyzed: S-wave velocity, D-wave velocity, a-wave velocity, Tmax velocity, PIV. Results were divided into sub-groups with reduced value, normal value and increased value and compared with fetal and neonatal condition. RESULTS: The relationship between the increased PIV value in the first trimester of pregnancy and an increased risk of chromosomal aberrations was observed, whereas the increased DV PI value in the second trimester of pregnancy with reduced A -wave were associated with a higher incidence of FGR. No correlation between the remaining DV blood flow velocities in the first and second trimester of pregnancy and the more frequent occurrence of fetal and neonatal complications has been confirmed. CONCLUSIONS: The increased DV PIV is a good prognostic tool for the detection of chromosomal aberrations in first trimester of pregnancy. In the second trimester, the increased DV PIV and the reduced A- wave velocity correlate with the fetal growth restriction. Ductus venosus seems to be an indirect indicator of intrauterine hypoxia with moderate prognostic value for adverse obstetric outcomes.

Prediction of preterm birth using PAMG-1 test: a single centre experience - preliminary report.

OBJECTIVES: Placental alpha microglobulin-1 (PAMG-1) is a novel biomarker detected in cervicovaginal discharge in patients threatened with preterm birth (PTB). This study aimed to show a single centre experience of assessment of imminent spontaneous PTB risk in patients with symptoms suggesting preterm labour (PTL). MATERIAL AND METHODS: The study group consisted of 46 women with singleton pregnancies between 24 + 0/7 and 33 + 6/7 weeks of gestation who presented with symptoms of threatened PTL, with cervical dilatation of < 3 cm, cervical length (CL) of < 30 mm and clinically intact fetal membranes. CL was measured via transvaginal ultrasound and the PAMG-1 test was performed in all of the objectives. RESULTS: Sensitivity (SN), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of prediction of PTB within seven days for CL were 100%, 11.11%, 5.88% and 100%, respectively. The PAMG-1 test SN, SP, PPV and NPV of the same endpoint were 50%, 80.56%, 12.5% and 96.67%, respectively. CONCLUSIONS: PAMG-1 is a more accurate predictor of PTB when compared to CL. Routine use of both mentioned tests could allow identification of low-risk patients and reduction of rate of unnecessary hospitalizations and treatments.

Amniocentesis in Twin Pregnancies: Risk Factors of Fetal Loss.

This study aims to determine if second trimester amniocentesis in twin pregnancies provides a significant independent contribution in the prediction of miscarriage or fetal loss at any stage of pregnancy. This was a retrospective cohort study of women with twin gestations booked for routine prenatal care in four fetal medicine units in Poland in the years 2010-2020. The study population included: (1) twin pregnancies that underwent amniocentesis at 16-20 weeks' gestation; (2) twin pregnancies that did not require any further testing and were followed-up routinely. Univariable and multivariable regression analysis was used to define which maternal and pregnancy characteristics provided a significant independent contribution in the prediction of miscarriage and fetal loss at any stage of pregnancy. In the study period, 2645 twin pregnancies were eligible for analysis. There were 144 cases of miscarriage defined as fetal loss of one or both twins before 24 weeks and 40 cases of intrauterine death of one or both twins after 24 weeks. A total number of 162 twin pregnancies underwent amniocentesis at 16-20 weeks' gestation. The rate of miscarriage before 24 weeks and the rate of fetal loss at any stage of pregnancy in the group that underwent amniocentesis was 10.49% and 13.58%, respectively, compared to 5.11% and 6.52% that did not undergo amniocentesis. Multivariable regression analysis showed that factors providing a significant independent contribution in the prediction of miscarriage and fetal loss at any stage of pregnancy were monochorionicity (MC), large intertwin discordance in crown-rump length (CRL), low Pregnancy Related Plasma Protein (PAPP-A) MoM and nuchal translucency (NT) above 95th centile. Amniocentesis in twin pregnancies does not provide a significant contribution in the prediction of miscarriage or fetal loss at any stage of pregnancy.

Evaluation of the Risk of Birth Defects Related to the Use of Assisted Reproductive Technology: An Updated Systematic Review.

Fertility problems constitute a serious medical, social, and demographic problem. With this review, we aim to critically appraise and evaluate the existing literature surrounding the risk of birth defects in offspring conceived using techniques based on assisted reproductive technology (ART). Based on searches of the literature in PubMed and ScienceDirect, we obtained a total of 2,003,275 works related to the topic. Ultimately, 11 original papers published in the last 10 years qualified for inclusion in the study. Based on five studies included in this analysis, it was shown that ART significantly increases the risk of congenital malformations in associated newborns. Due to the specifics of given studies, as well as potential confounding risk factors, this influence cannot be ignored. Therefore, considering the information contained in the articles included in this systematic review, it was determined that the risk of birth defects is not directly related to the use of ART itself but also depends on the age of partners, causes of infertility, comorbidities, and the number of fetuses during a pregnancy, as well as many other factors not covered in the literature. It is thus necessary to impress upon infertile couples who wish to have offspring that the use of ART is not risk-free but that the benefits outweigh the risks. Further education in this field, as well as social understanding, is also required.

Birth Weight < 3rd Percentile Prediction Using Additional Biochemical Markers-The Uric Acid Level and Angiogenesis Markers (sFlt-1, PlGF)-An Exploratory Study.

(1) Aim: Ultrasound is the gold standard for assessing fetal growth disorders. The relationship between high sFlt-1/PlGF scores and LBW (low birth weight) was described. In this study, we attempted to assess whether uric acid could be used as a secondary marker in estimating the pregnancy risk associated with LBW. (2) Material and methods: 665 pregnant women with a suspected or confirmed form of placental insufficiency were enrolled. In each of the patients, sFlt-1 and PlGF and uric acid levels were determined. Patients were divided into two groups according to birth weight below and above the third percentile for the given gestational age with the criteria of the neonatal definition of FGR (fetal growth restriction). (3) Results: A significant negative correlation between neonatal birth weight and the uric acid level across the entire study group was observed. We found a significant negative correlation between neonatal birth weight and the uric acid level with birth weights < 3rd percentile. (4) Conclusions: There is a significant link between the uric acid concentration and LBW in the group with placental insufficiency. Uric acid can improve the prediction of LBW. An algorithm for LBW prognosis that makes use of biophysical (ultrasound) and biochemical (uric acid level, angiogenesis markers) parameters yields better results than using these parameters separately from each other.

Effectiveness of Different Algorithms and Cut-off Value in Preeclampsia First Trimester Screening.

Results: For the cut-off point >1 : 150, 86 women at an increased risk of eo-PE using algorithm 1 were identified. Of these 86 patients, 83 (96%) were identified using algorithm 2, 62 (72%) using algorithm 3, and 60 (69%) using algorithm 4. In addition, it was demonstrated that between 21% and 29% of women at a low risk of eo-PE could be given acetylsalicylic acid if a screening test was used that did not account for PlGF. Conclusions: In order to provide the highest level of health care to pregnant women, it is extremely important that full screening for eo-PE should be ensured. The cheapest algorithm based only on MAP and UtPI resulted in our patients being unnecessarily exposed to complications.

Implementation of the Publicly Funded Prenatal Screening Programme in Poland during the COVID-19 Pandemic: A Cross-Sectional Study.

The COVID-19 pandemic in 2020 affected the entire healthcare system in Poland, causing medical personnel to be relocated to other duties and limiting patients' contacts with healthcare professionals. A large part of the planned diagnostics and treatment was delayed due to lack of equipment and personnel. Against this background, we analysed the implementation of the publicly funded prenatal screening programme (PSP) in Poland compared to the previous year. This is a cross-sectional study. We used nationwide datasets on the implementation of the prenatal testing programme over the period 2019−2020, datasets from the Statistics Poland on birth and the data on the development of the COVID-19 epidemic in Poland. In the year 2020, we observed a 12.41% decrease in woman enrolled to the programme compared to 2019. However, the decrease concerned only women under 35 years of age. With respect to the number of deliveries in the calendar year, the number of patients enrolled in the programme decreased by 3% (31% vs. 34%, p < 0.001). We also observed an increase in estriol measurements per the number of patients included in the programme, and a reduction in the number of PAPP-A tests in the first trimester, which proves an increased share of the triple test in the prenatal diagnosis of chromosomal aberrations. With respect to the number of deliveries, the number of amniocentesis procedures performed under PSP decreased by 0.19% (1.8% vs. 1.99%, p < 0.0001). In 2020, compared to the previous year, the number of patients included in the prenatal testing programme in Poland decreased. In terms of the number of births in Poland, the number of integrated screening tests also decreased, at the expense of increasing the percentage of triple tests. There were also significant reductions in the number of invasive diagnostic tests.

First-Trimester Fetal Hepatic Artery Examination for Adverse Outcome Prediction.

OBJECTIVE: To assess whether there are differences in first-trimester fetal hepatic artery flows depending on pregnancy outcomes. METHODS: The prospective study conducted in 2012-2020 included 1841 fetuses from singleton pregnancies assessed during the routine first-trimester ultrasound examination (between 11- and 14-weeks' gestation). Also, each fetus was examined to determine their hepatic artery flows by measuring the artery's pulsatility index (HA-PI) and peak systolic velocity (HA-PSV). RESULTS: The fetuses that were classified as belonging to the adverse pregnancy outcome group (those with karyotype abnormalities and congenital heart defects) were characterized by a significantly lower HA-PI and higher HA-PSV compared to normal outcome fetuses. CONCLUSION: Hepatic artery flow assessment proved to be a very useful tool in predicting adverse pregnancy outcomes, in particular karyotype abnormalities and congenital heart defects.

The Polish Society of Gynecologists and Obstetricians Guideline for the diagnostic assessment and management of multiple-gestation pregnancy complicated by fetal growth restriction.

The aim of the Guideline is to unify the diagnostic-therapeutic management of multiple-gestation pregnancies complicated by fetal growth restriction in at least one fetus.

Risk Assessment of the Increased Occurrence of Congenital Cardiac and Non-Cardiac Defects in Fetuses with a Normal Karyotype after Assisted Fertilization in Comparison to Natural Fertilization Based on Ultrasound Diagnostics.

The goal of the study was to assess changes in parameters based on ultrasound examinations-these were Crown Rump Length (CRL), Nuchal Translucency (NT), Fetal Heart Rate (FHR), and Pulsatility Index for Ductus Venosus (DV-PI)-in the first trimester of pregnancy in women in which there was a natural initiation of the pregnancy due to spontaneous ovulation, women in which the pregnancy was initiated as a result of stimulated ovulation, as well as in the group in which pregnancy was achieved through the use of In-Vitro Fertilization (IVF)-assisted reproduction. A total of 1581 women became pregnant without the use of assisted reproduction methods. Out of 283 pregnancies, in 178 patients, induced ovulation was utilized. Next, 137 women had sexual intercourse and became pregnant; 41 of them became pregnant through Intrauterine Insemination (IUI) as a result of Artificial Insemination by Husband (AIH), and 13 became pregnant after Artificial Insemination by Donor (AID). The third group consisted of 105 women subjected to Controlled Ovarian Hyperstimulation (COH). In this group of pregnant women, 53 pregnancies were resultant of Intracytoplasmic Sperm Injection (ICSI), and 52 pregnancies were the result of Intracytoplasmic Morphologically selected Sperm Injection (IMSI). The obtained results did not indicate that the chosen method of fertilization or the chosen ovulation method had a statistically significant effect on the development risk of congenital heart or non-heart defects in the fetus.