Роль прозапальних цитокінів у патогенезі передчасної пологової діяльності при багатоплідній вагітності, яка настала внаслідок застосування допоміжних репродуктивних технологій

Continuous quality improvement and assisted reproductive technology multiple gestations: some progress, some answers, more questions

The effective prevention of multiple pregnancies by elective single embryo transfer

During the past 20 years, the prevalence of Down syndrome (DS) has increased with the increase in mean maternal age. The prevalence of multiple births has also increased because of older maternal age and use of assisted reproductive technologies. This study was designed to determine the maternal age–specific prevalence of DS in monozygotic and dizygotic pregnancies, assess risk relative to singleton pregnancies, as well as compare prenatal diagnosis and pregnancy outcomes for DS fetuses in multiple and singleton pregnancies. The database of the European Surveillance of Congenital Anomalies includes live-born congenital anomaly cases, stillborn cases and fetal deaths after 20 weeks’ gestation, as well as prenatally diagnosed cases resulting in termination of pregnancy for fetal anomaly. The study population consisted of 14,827,105 pregnancies between 1990 and 2009, of which 2.89% were multiple gestations. Individual fetuses/babies with DS from multiple and singleton pregnancies were considered “cases.” Twin pairs with both twins having DS were “concordant” pairs. Relative risk (RR) with the 95% confidence interval (CI) was used to estimate the prevalence of cases with DS among multiple births relative to that among singleton births. From 1990 to 1999, the total corrected prevalence of DS cases from multiple pregnancies as opposed to singleton pregnancies per 10,000 births was 0.40 (95% CI, 0.36–0.45), rising to 0.47 (95% CI, 0.42–0.53) in 2000 to 2009 (P > 0.05). Overall (1990–2009), the prevalence of DS cases per 10,000 multiple births was 15.1 (95% CI, 14.6–15.9); and per 10,000 singleton births, 20.1 (95% CI, 19.9–20.3). The prevalence of DS cases per 10,000 multiple births rose with age of 44 years or younger, after which it was considerably lower. The adjusted RR of DS for babies from multiple births relative to singleton births was 0.58 (95% CI, 0.53–0.62). Of 19,397 babies born to mothers older than 44 years, 2043 (10.5%) were from multiple births. Only 1 fetus from a multiple pregnancy was a DS case, a prevalence of 4.48 (95% CI, 0.67–35.1) per 10,000 multiple births, compared with 562 singleton DS cases, a prevalence of 327 (95% CI, 301–356) per 10,000 singleton births (RR, 0.015; 95% CI, 0.002–0.107). In 8.7% (n = 54) of affected pairs, the twins were concordant for DS, 51 same-sex twin pairs and 3 unlike-sex twin pairs. The maternal age–adjusted RR of a monozygotic pregnancy being affected was 0.34 (95% CI, 0.25–0.44) compared with singleton pregnancies. No affected monozygotic twin pregnancies occurred in the group older than 44 years. For dizygotic pregnancies, the maternal age–adjusted RR of at least 1 twin being affected was 1.34 (95% CI, 1.23–1.46) compared with singleton pregnancies. For age older than 44 years, the RR was 0.04 (95% CI, 0.01–0.27). The proportion of DS cases prenatally diagnosed was lower for multiple than for singleton pregnancies at all maternal ages, for an overall maternal age–adjusted odds ratio (OR) of 0.62 (95% CI, 0.50–0.78). The overall proportion of termination of pregnancy for fetal anomaly cases from multiple pregnancies was lower than singletons at every maternal age, giving an overall maternal age–adjusted OR of 0.52 (95% CI, 0.41–0.65). Down syndrome cases from multiple births were not more likely to be stillbirths/fetal deaths than from singleton births; the maternal age–adjusted OR was 1.03 (95% CI, 0.59–1.78). Individual fetuses from twin pregnancies are at lower risk for DS than those from singleton pregnancies. The estimates of the lower maternal age–specific DS risk in twin pregnancies, combined with the clinician’s knowledge of zygosity/chorionicity and maternal age at ovulation for women having assisted reproductive technologies, should allow more accurate risk estimates for genetic counseling and prenatal screening.

The objective: conduct a comparative clinical and statistical analysis of obstetric and perinatal complications in singleton and multiple pregnancies after assisted reproductive technologies (ART) according to archival documents (pregnancy observation data and birth history) and identify features of multiple pregnancy. Materials and methods. During the period 2017–2019, 522 women gave birth in maternity hospital «Leleka» after assisted reproductive technologies, 331 women were observed in the maternity hospital «Leleka». 445 women gave birth with a singleton pregnancy and 77 with a multiple pregnancy. A clinical and statistical analysis of 150 pregnancy and childbirth histories was performed. All pregnant women were divided into two groups: Group I – 75 pregnant women with singleton pregnancies after ART; Group II – 75 pregnant women with multiple pregnancies after ART. The selection criteria for comparative clinical and statistical analysis were women whose pregnancies occurred as a result of ART, namely by in vitro fertilization (IVF) using five-day frozen embryos. Mathematical research methods were performed in accordance with the recommendations of O.P. Minzer (2013). The reliability of the cancellation of the mean pairs was calculated using the Student’s and Fisher’s criteria. Graphs were designed using the program «Microsoft Excel». Results. Complications of early pregnancy in multiple pregnancies were: anemia (47.8% vs. 22.9%; p<0.01), placental dysfunction (43.3% vs. 22.9%; p<0.01), the threat of abortion (41.8% vs. 28.6%; p<0.01). Complications of the second half of pregnancy: preeclampsia (52.7% vs. 20.6%; p<0.01), fetal growth retardation (20.0% vs. 7.4%; p<0.01), gestational anemia (76,4% vs. 32.4%; p<0.01), placental dysfunction (47.3% vs. 22.1%; p<0.05). Complications in childbirth in women with multiple pregnancies were as follows: premature rupture of membranes (30.9% vs. 10.3%; p<0.05), anomalies of labor activity (16.4% vs. 5.9%; p>0.05), fetal distress (29.1% vs. 14.7%; p<0.05), premature placental abruption (3.6% vs. the absence of this indicator in group I). In patients of group II with multiple pregnancies 3.7 times more often the pregnancy ended prematurely compared with singleton (21.8% vs. 5.9%; p<0.05). Early preterm births predominated, of which births occurred in 3.6% of cases at 22–28 weeks, 7.3% at 28–32 weeks, and 6.4% at 32–34 weeks. Significant increase in the frequency of 32.7% of abdominal births in multiple pregnancies against 11.8% of patients in pregnancy with a single fetus (p<0.01). The structure of indications in patients of group II was as follows: severe preeclampsia 27.8%, development of fetal growth retardation and fetal distress of 11.1%, respectively, premature placental abruption 16.7%, the following single indications (pelvic presentation of the fetus, transverse or oblique position of the fetus, clinically narrow pelvis, abnormalities of labor, scar on the uterus) – 33.3%. Significant increase in the total frequency of neonatal asphyxia of varying severity in multiple pregnancies (35.0% vs. 5.9%; p<0.05), fetal growth retardation (27.3% vs. 11.8%; p<0.01). Conclusions. Multiple pregnancies are a high risk factor for gestational anemia, preeclampsia, placental dysfunction, early fetal growth retardation, and fetal distress during pregnancy and childbirth. This causes a high level of abdominal delivery. Therefore, further research to predict and prevent obstetric and perinatal complications in multiple pregnancies after ART is relevant today. Keywords: obstetric and perinatal complications of pregnancy, multiple pregnancy, assisted reproductive technologies.

Hemoglobin concentration in multiple versus singleton pregnancies — retrospective evidence for physiology not pathology

After completing this article, readers should be able to: 1. Describe the outcomes of assisted reproductive technologies (ART) for singleton, twin, and other multiple births. 2. Describe the role of fertility in adverse outcomes seen with ART births. 3. Review the association of birth defects with ART. 4. Delineate the association of disease of genomic imprinting with ART. 5. Describe the relationship between ART and the subsequent incidence of neurodevelopmental sequelae. In the 1977 ruling “Carey v. Population Services International,” the United States Supreme Court ruled that the decision to bear children is constitutionally protected. (1) Significant interest already had been shown in the development and improvements of in vitro fertilization (IVF) for infertile couples. The first human pregnancy and human birth using IVF were reported by Steptoe and Edwards in the United Kingdom. (2) Their work resulted in the first baby born via reproductive technologies, Louise Brown, born on July 25, 1978, at Oldham General Hospital in Oldham, United Kingdom. (3) She was born via a planned cesarean section, and her birthweight was 2.61 kg. The first successful viable IVF in the United States was performed by Jones and Seager-Jones in 1981 in Norfolk, Virginia. (4) Assisted reproductive technologies (ART) have seen a recent surge in popularity. The Centers for Disease Control and Prevention (CDC) reported that 122,872 cycles of ART were initiated in 2003, resulting in the delivery of 48,756 neonates, (5) accounting for approximately 1% of all neonates delivered in the United States. The percentage is higher in many countries, including Denmark, where it is estimated that 5% of all deliveries are with the assistance of ART. (6) Couples pursue ART for myriad reasons, including tubal transport factors, ovulatory dysfunction, uterine factors, endometriosis, male- and female-specific factors, and when a cause of infertility is unknown. (5) It would be very …

Neonatal outcomes of antenatal corticosteroids in preterm multiple pregnancies compared to singletons.

The aim: To carry out a comparative statistical analysis of obstetric and perinatal complications in singleton and multiple pregnancies once assisted reproductive technologies (ART) are applied according to the records taken from archival materials (maternity and delivery records) and identify the clinical features of multiple pregnancy. Materials and methods: Over the period of 2017-2019, 522 women gave birth in LELEKA Maternity Hospital LLC after using assisted reproductive technologies and 331 women among them were followed-up in the women's health center of LELEKA maternity hospital. Among these women (522) with singleton pregnancy 445 women gave birth, while in multiple pregnancy - 77. The statistical analysis of 150 maternity and delivery records was carried out. All pregnant women were divided into two groups: group 1 - 75 women having singleton pregnancy after ART; group 2 - 75 women having multiple pregnancy after ART. Women getting pregnant after ART, or in vitro fertilization (IVF) and five-day frozen embryo transfer to be exact, turned out to be the selection criterion for a comparative statistical analysis. Mathematical methods for research were used as O.P. Mintser (2013) suggested. The reliability of the digit cancellation test was calculated using the Fisher's exact test and Student's T-test. Graphs were designed using Microsoft Excel. Results: The complications of early multiple pregnancy were the following: anemia (47.8% as opposed to 22.9%, p<0.01), placental insufficiency (43.3% in contrast to 22.9%, p<0.01), threatened abortion (41.8% in contrast to 28.6%, p<0.01). The complications in late pregnancy are as follows: preeclampsia (52.7% as opposed to 20.6%, p <0.01), intrauterine growth restriction (20.0% as opposed to 7.4%, p <0.01), anemia in pregnancy (76.4% in contrast to 32.4%, p<0.01), placental insufficiency (47.3% in contrast to 22.1%, p<0.05). Conclusions: Multiple pregnancy is a high risk for anemia in pregnancy, preeclampsia, placental insufficiency, early intrauterine growth restriction and fetal distress in pregnancy and labor. It predetermines the high level of a caesarean section. Therefore, further research aimed at prediction and prevention of obstetric and perinatal complications in multiple pregnancy after ART is currently topical.

Hormonal disorders are one of the main known causes of miscarriage and preterm birth in multiple pregnancies resulting from assisted reproductive technology (ART). Progesterone and the number of its receptors play an important role in the preservation and prolongation of pregnancy and it is the pressing issue of our time. The study of placentas, as the main site of synthesis of progesterone, has high informative potential and it is the most important diagnostic object, and information received by its research is essential for the full conclusion on the causes, mechanisms, close and long-term effects of multiple pregnancy pathology. Aim. The aim of our study was to investigate immunohistochemical features of placentas from women with dichorionic diamniotic twin pregnancies in spontaneous fertilization and after use of assisted reproductive technology (ART). Methods and results. According to this goal we examined 94 women, 44 of whom had multiple pregnancies due to ART, 42 with separate multiple pregnancy and 38 women with a singleton pregnancy. We carried out clinical and statistical analysis of the course of pregnancy and childbirth in the studied groups. During the study it was found that multiple pregnancies due to assisted reproduction belong to the high risk of gestation, at which premature births occur much more frequently than in singleton pregnancies. We were the first to carry out the immunohistochemical study of placentas in which the highest expression of progesterone receptors in the nuclei of cells of decidua (45%) related to the parent structure of the placenta from women with multiple pregnancies caused by ART is found. It is also found that with increasing gestational age, there has been a significant decrease in the expression of the activity of progesterone receptors (from 45 to 2.5%), regardless of the method of conception and the number of fetuses. Conclusions. The results of the study point to the definitive link of structures of placental-endometrial relations as an important component of the appropriateness of hormone therapy.

While various policies to support couples experiencing infertility have been introduced due to the fertility rate rapidly dropping in developed countries, few large-scale nationwide cohort studies have evaluated the outcomes of assisted reproductive technology (ART) health insurance coverage policies. To evaluate ART health insurance coverage for multiple pregnancies and births in Korea. This population-based cohort study used delivery cohort data from the Korean National Health Insurance Service database between July 1, 2015, and December 31, 2019. A total of 1 474 484 women were included after exclusion of those who gave birth at nonmedical institutions and those with missing data. Two 27-month periods were examined before and after the Korean National Health Insurance Service had begun covering ART treatment (preintervention period, July 1, 2015, to September 30, 2017; postintervention period, October 1, 2017, to December 31, 2019). Multiple pregnancies and multiple births were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes. Total births were defined as the total number of babies born to each pregnant woman during the follow-up period. An interrupted time series with segmented regression was conducted to analyze the time trend and its change in outcomes. Data analysis was conducted between December 2, 2022, and February 15, 2023. Of the 1 474 484 women eligible for the analysis (mean [SD] age, 33.2 [4.6] years), approximately 1.60% had multiple pregnancies and 1.10% had multiple births. After covering ART treatment, the likelihood of multiple pregnancies and multiple births was estimated to increase by 0.7% (estimate, 1.007; 95% CI, 1.004-1.011; P < .001) and 1.2% (estimate, 1.012; 95% CI, 1.007-1.016; P < .001) compared with before coverage. The probability of an increase in the number of total births per pregnant woman after the intervention was estimated to be 0.5% (estimate, 1.005; 95% CI, 1.005-1.005; P < .001). The relatively high-income class above the median income showed a decreasing trend in multiple births and total births before the intervention, but after the intervention, a significant increase was observed. This population-based cohort study found that the possibility of multiple pregnancies and births in Korea significantly increased after the implementation of an ART health insurance coverage policy. These findings suggest that the development and coverage of policies to support couples experiencing infertility may help address low fertility rates.

Background: The global rise in pregnancies following assisted reproductive technology (ART) use has prompted ongoing evaluations into the impact of this technology on maternal and neonatal outcomes. Thus, this study aimed to compare outcomes between ART-conceived pregnancies and spontaneously conceived pregnancies, stratified by singleton and multiple pregnancies. Methods: We conducted a single-center retrospective cohort study at Gyeongsang National University Changwon Hospital in South Korea, using the medical records of women who delivered between January 2023 and December 2024. A total of 921 pregnancies were included, comprising 816 singleton pregnancies and 105 multiple pregnancies. Maternal and neonatal baseline characteristics were compared between ART-mediated and spontaneous conceptions within each gestational category. Outcomes assessed included postpartum hemorrhage (PPH), preterm birth (PTB), small for gestational age (SGA), neonatal intensive care unit (NICU) admission, 5-minute Apgar score &lt; 7, and neonatal death. Multivariable logistic regression was performed to estimate adjusted odds ratios (aORs), controlling for relevant confounders. Results: Most maternal and neonatal outcomes did not significantly differ between ART-mediated and spontaneous conceptions in either singleton or multiple pregnancies. There were no statistically significant differences in the rates of PTB, SGA, NICU admission, low 5-minute Apgar score, and neonatal death between the groups. However, there was a significantly higher incidence of PPH in ART-conceived singleton pregnancies (25.7% vs. 9.4%), which remained significant in the multivariable analysis (aOR: 3.64, 95% confidence interval (CI): 2.21–5.98; p &lt; 0.001). No significant difference in PPH incidence was observed in the multiple pregnancy cohort. Conclusions: Overall, most outcomes were comparable between ART-mediated and spontaneous conceptions. However, ART-conceived singleton pregnancies showed a significantly higher risk of PPH, even after adjusting for confounders. These findings underscore the need for heightened surveillance for PPH in ART-mediated singleton pregnancies, even in the absence of other risk factors.

Introduction. In assisted reproductive technology pregnancy (ARTP), the most unfavorable factor affecting perinatal outcomes is iatrogenic multiple gestation. Active introduction into practice of techniques that reduce the risk of multiple pregnancy, on the one hand, and management of ARTP in specialized medical centers with experience in working with this category of patients, on the other, can improve perinatal outcomes. Aim. Analysis of perinatal outcomes in assisted singleton and multiple pregnancies in order to assess the contribution of the multiple gestation factor to adverse health outcomes for newborns, and its relevance for improving of assisted reproductive technology. Materials and methods. A retrospective study of the ante-, intra- and early neonatal period was carried out in 672 infants born at the Medical Center AVICENNA (Novosibirsk) for the period from 2006 to 2015. The total sample was divided into 3 groups: 1st – infants from singleton ARTP (n = 345); 2nd – infants from multiple ARTP (n = 177); 3rd – infants from singleton spontaneous pregnancy (SSP) (n = 150) without infertility in the parental history, gravidity and parity were equal. A clinical and anamnestic method was used, with an assessment of the main parameters of the health status of infants and parents. Results. It was revealed that complications such as threatened miscarriage and preterm labor, cervical insufficiency, preeclampsia, and placental disorders are diagnosed significantly more often in multiple ARTP (p &lt; 0.001) compared with singleton ARTP. At the same time, in the setting of a specialized center, the majority of infants from ARTP were full-term, both in singleton (94.5% of cases) and in multiple (52.5% of cases) pregnancies. Any assisted reproductive technology pregnancy belongs to the group of high obstetric risk, but timely correction of complications significantly improves perinatal outcomes. Conclusion. ARTP belongs to the group of high obstetric risk, which increases significantly with multiple gestation. Management of an infertile couple in a specialized center with continuity at all stages from the moment of contacting the clinic to the birth of a child allows, despite the development of complications, to ensure the birth of full-term infants (both in singleton and multiple pregnancies), and in singleton pregnancies it leads to the birth of children, in main health indicators similar to those from a spontaneous pregnancy.

Do assisted reproductive technologies cause adverse fetal outcomes?

IntroductionThe purpose of the present study was to estimate the effect of fertility treatment; both assisted reproductive technology (ART) and non-ART ovulation stimulation, on the number and rate of multiple...

When Darine El-Chaar began her residency in obstetrics and gynecology at the University of Ottawa five years ago, she grew curious about the potential health repercussions of assisted reproductive technologies (ART), the catchall term for procedures used to help couples artificially conceive a child. ART involves surgically removing eggs from a woman’s ovaries, combining them with sperm in the laboratory, and returning them to the womb.1 Women undergoing ART take “fertility drugs” such as clomiphene citrate and gonadotropins to stimulate the production of many eggs rather than the single egg that would normally grow during their monthly menstrual cycle.2 El-Chaar wondered about the influence that ART procedures, as well as the underlying infertility itself, might have on the health of children conceived. She is one of many researchers working to answer the fundamental question of whether introducing fertility drugs and manipulating eggs and sperm in a laboratory setting—in essence, altering the primal environment—sets the stage for adverse health effects in children. Artist’s rendering of intracytoplasmic sperm injection, in which a single sperm is inserted into an egg. Although some research indicates such a risk exists, there haven’t been enough large-scale studies to ascertain if the potential effects are severe enough over the long term to deter couples from seeking infertility treatments. Meanwhile, some findings are pointing the way toward possible refinements to improve health outcomes for ART babies.