The development of higher mental functions of children born with intracytoplasmic sperm injection, compared with in vitro fertilization

Surkova Karolina Leonidovna ORCID: 0000-0001-7501-0535 Researcher; Department of Medical Psychology; Scientific Center for Mental Health Kashirskoe shosse, 34, Moscow, 115522, Russia www1-11@narod.ru

Zvereva Natal'ya Vladimirovna ORCID: 0000-0003-3817-2169 PhD in Psychology Professor; Faculty of Clinical Psychology; Moscow State Psychological and Pedagogical University Leading Researcher; Federal State Budgetary Scientific Institution 'Scientific Center for Mental Health' Kashirskoe shosse, 34, Moscow, 115522, Russia nwzvereva@mail.ru

Introduction

With the birth of the first artificially conceived child in 1978, the use of assisted reproductive technologies (ART) has increased significantly. This raises important discussions about the possible long-term effects of ART on future generations ^[1,2,3,4,5]. Modern research shows diverse and contradictory data. Some studies mention increased risks of behavioral, emotional, and cognitive difficulties in children conceived with ART (Sutcliffe, Ludwig, 2007; Norman, Hart, 2013; Spangmose, 2017; and others) ^[6,7,8], mental disorders (Carson, 2015) ^[9], which can be compensated by as the child grows up (Bakhtiyarova, 1993; Atlasov, 2004; Evstyukova, 2005; Plaksina, 2011; and others) ^{[10,11,12,13]}. Some studies have noted that cognitive deficits were more common among children conceived by ICSI than in IVF children (Knoester, 2008) ^[14]. Interdisciplinary studies have shown a wide range of indicators of mental development among artificially conceived children, ranging from high levels of intellectual development to severe disabilities ^{[15,16,17,18]}.

The IVF method consists of fertilizing an egg outside a woman's body. The germ cells of men and women are combined in a Petri dish, after which they are placed in a special incubator, the conditions of which promote the development and maturation of embryos. Unlike IVF, ICSI technology is an invasive procedure in which spermatozoa are selected by a specialist and injected into an oocyte using a microinjection technique, which bypasses many natural selection barriers. Considering that direct manipulation of the oocyte during fertilization using the ICSI method can theoretically have a long-term effect on the development of a child, the formation of higher mental functions in children conceived by this method should be carefully studied in comparison with other methods of fertilization. It is important to emphasize that not only the method of fertilization, but also many other factors, such as the age of the mother, the state of health of the parents and other influences, can contribute their own unique nuances to the development of the child.

The purpose of our study was to study the development of higher mental functions in children aged 3 to 8 years, conceived using IVF and ICSI procedures, in comparison with the control group (spontaneously conceived peers).

Attention is focused on the analysis of various aspects of artificial insemination, the characteristics of the sample of artificially conceived children are given: the method of fertilization, the number of embryonic transplants performed, the protocol for the transfer of reproductive material (cryoprotocol / fresh cycle), the features of the course of pregnancy and the state of health of the child at birth.

The subject of the study was the consideration of the features of the cognitive development of children conceived by various reproductive technologies. The theoretical and methodological basis of this study is the concept of L.S. Vygotsky and A.R. Luria concerning the systemic dynamic localization of higher mental functions. Special attention is paid to the heterochronous maturation of morphofunctional brain regions in children and the evolution of higher mental functions. The theoretical aspects ^{[4,7,11,12,17]} concerning the peculiarities of the development of children conceived with the help of assisted reproductive technologies are being investigated. The use of a neuropsychological approach and diagnostic tools in assessing the mental activity of preschool and primary school age children is the methodological basis of the study.

Scientific novelty. The presented work offers a new perspective on the specifics of development and further compensation for disorders of higher mental functions in children conceived with the help of ART. The article examines the impact of various types of artificial insemination procedures on the risks of functional developmental disability of a child in the future. An analysis of the results of the study allowed us to hypothesize the phenomenological development of higher mental functions in children conceived through ART. The results of the neuropsychological examination revealed both the features of the development of mental functions common to all participants, as well as the specifics characteristic of children conceived with the help of assisted reproduction.

Materials and research methods

The study involved 115 children aged 3 to 8 years; of these, 31 children were conceived using IVF, 23 children were conceived using ICSI, and 61 children formed the natural conception control group. The study was conducted on an outpatient basis on the basis of the Federal State Budgetary Budgetary Institution of the Russian Academy of Medical Sciences. The study was conducted in accordance with the Code of Ethics of the Russian Psychological Society (2012), as well as in accordance with Federal Law No. 152-FZ dated 27.07.2006 "On Personal Data". Before starting the study, the child's official representatives signed a document confirming their voluntary informed consent to participate in the study. The inclusion criteria were children conceived with ART at the age of 3-8 years. The study was conducted from 2019 to 2024.

The research method was the analysis of anamnestic data on the child's development, as well as the collection of detailed information about the procedures performed during the planning and implementation of the artificial insemination protocol.

Neuropsychological techniques developed by A.R.Luria-L.S.Tsvetkova and adapted to childhood by other authors ^[19,20] were used to study the development of higher mental functions (motor sphere, attention, thinking, memory, perception) in preschool and primary school children. To assess the severity of dysfunctional development, a three–point scale was used, where 1 point means no symptoms of dysfunctional development; 2 – symptoms of dysfunctional development are poorly expressed; 3 – symptoms of dysfunctional development are expressed.

Statistical processing of the data obtained during the study was carried out using the nonparametric Mann-Whitney criterion and Spearman's rank correlation coefficient.

The results of the study

An analysis of anamnestic data revealed that among children conceived using in vitro fertilization (100%=31 children), 42% have conditionally normative development at various stages of ontogenesis. At the same time, 48% of babies have various negative factors, including intrauterine hypoxia, asphyxia of newborns, perinatal encephalopathy and others, which have a depressing effect on their further cognitive development. 10% of children in this group conceived by IVF have disorders that manifest themselves at various stages of ontogenesis, which leads to pronounced problems in mental development and the inability to achieve full compensation for intellectual deficits.

Among children conceived using the ICSI method (100%=23 children), as well as among those who were born spontaneously (100%=61 children), there were no noticeable aggravating factors of the intrauterine and perinatal periods that could affect their mental development. In 65% of cases, ICSI-conceived children showed normal anamnestic indicators, while 35% had various negative factors (prematurity, viral diseases of the mother during the first trimester, the threat of termination of pregnancy, etc.) that could have an impact on their health and development.

A clinical analysis of naturally conceived children, who made up 100% of the sample (61 people), revealed that 68% of them have aggravating factors of ontogenetic development. In 29% of the children, the anamnestic parameters were within the conditional norm.

Let's consider additional anamnestic information of the children who participated in the study in Table 1.

Table 1 - Anamnestic data of children participating in the study

Comparing the anamnestic data of children conceived with IVF and ICSI, we find that in the case of IVF, in most cases, fertilization occurs from the first to the third attempt, and with the ICSI method, the process often requires longer efforts — the number of embryonic implantations can vary (from one attempt to 6-8 or more). The embryo cryotransference protocol prevails in two reproductive methods of artificial insemination. This is due to the fact that when transferring into the uterine cavity, one embryo is often transplanted, and the remaining embryos obtained as a result of cultivation are cryopreserved in case of repeated artificial insemination.

Delivery in the case of an induced pregnancy is mostly completed by caesarean section, while self-delivery prevails in the case of a naturally occurring pregnancy. Prematurity occurs in approximately the same cases both among artificially conceived children and with ES.

A qualitative analysis showed that among children conceived with IVF, the risk of functional insufficiency in the development of cognitive functions is higher than among children conceived using ICSI and EZ.

Figure 1 shows the average data on the severity of functional insufficiency in the development of higher mental function among children from induced pregnancy in comparison with the control group of spontaneously conceived children.

Figure 1 - Average indicators of the severity of the dysfunctional development of higher mental function in children during artificial and natural conception. Along the axis of the abscissa, the severity of the symptoms of functional insufficiency. On the ordinate axis: IVF - data on the group of children conceived by IVF; ICSI – data on the group of children conceived by ICSI; EZ – data on the group of children of natural conception

It follows from Figure 1 that in the study group of children conceived with IVF, there are signs of functional insufficiency of certain types of attention. These children face difficulties in completing tasks for stability and attention distribution, showing rapid fatigue and difficulty in getting involved in tasks. Such symptoms may signal abnormalities in the functioning of subcortical structures. ICSI-conceived children also experience similar difficulties in attention processes, although the symptoms of exhaustion and attention distribution are less pronounced. Among spontaneously conceived children, attention functions remain within the normal range, although there are mild difficulties in switching attention from one task to another. The functions of memory, thinking, and perception in both artificially and spontaneously conceived children generally correspond to conditionally normative development. However, speech development and motor disorders are noticeable in the IVF group of children.: they manifest themselves in the form of symptoms of impaired muscle tone, oral praxis, phonetic-phonemic perception and lexico-grammatical structure of speech, difficulties in sound pronunciation, insufficiency of general kinetic praxis. Among children conceived by ICSI and EZ, symptoms of mild phonetic perception deficiency are more common.

Psychological analysis of neuropsychological examination data showed that children from induced pregnancy, especially those conceived by IVF, face more pronounced difficulties in the development of certain higher mental functions, such as attention, motor sphere and general speech development.

A comparative analysis of cognitive development among children conceived by IVF and ICSI, using statistical data processing, revealed twelve significant differences (Table 2), the results of which indicate an under-development of some components of mental activity.

Table 2 - Comparison of indicators of components of mental activity among children conceived using various assisted reproductive methods

Differences in the cognitive development of children conceived using various methods of reproductive technologies are clearly manifested in the frequency of disorders. Children conceived by IVF are more likely to show a more noticeable functional insufficiency of the energy factor (EF) at the level of stem structures, and are also susceptible to impaired attention, general motor practice, auditory-speech memory, and visual perception. Their thinking, both visually imaginative and visually effective, as well as the development of impressive speech show significant difficulties in understanding the plot picture and composing a story based on it, the ability to generalize abstract concepts and correlate objects according to their properties. The comparative analysis takes into account the comorbidity of cognitive disorders, while the revealed dysfunction of one mental function can both create conditions and cause the insufficiency of another function.

We investigated the potential impact of the number of hookups on the cognitive development of children born as a result of IVF and ICSI. Table 3 illustrates the correlation between the number of transplants performed before conception and indicators of the development of higher mental functions among artificially conceived children.

Table 3 - Correlation analysis of the number of embryonic transplants performed before pregnancy and indicators of the development of higher mental functions in children conceived by IVF and ICSI (p<0,01**; p< 0,05*)

The difference in the revealed correlations between children born as a result of IVF and ICSI indicates a blurred relationship between the number of transplants performed and the risks of dysontogenic development. It was not possible to establish any consistent indicators of mental activity, which casts doubt on the unambiguity of the influence of the chosen method of fertilization on the subsequent development of the child. However, a qualitative analysis of the data indicates that, despite the absence of direct correlations, there is still an indirect relationship between these phenomena.

Cryoprotocol involves the use of thawed reproductive material, whether it is embryos, oocytes or spermatozoa. The transfer of fresh embryos is usually carried out on the fifth day after the collection of biological material and subsequent cell culture to the blastocyst stage. As part of our research, we focused on analyzing the consequences of embryo cryotransfer.

When comparing the indicators of cognitive development and methods of embryonic transfer, four significant differences in the features of auditory and tactile perception were identified (Table 4).

Table 4 - Comparative analysis of cognitive indicators among children depending on the method of embryo transfer

From Table 4, we can note that the results of children conceived using cryotransfer ART, according to some indicators of mental development, exceed those of transfers carried out in a fresh cycle. It can be logically assumed that after cryopreservation of the embryo, optimal cellular recovery occurs, which not only enhances implantation abilities, but also affects the future mental potential of the child.

Discussion of the results. The results highlight the uniqueness of the cognitive development of children conceived with ART compared to those who were conceived naturally, where the chosen method of artificial insemination is important. It is observed that among ICSI children, the indicators of mental activity are higher than in children born thanks to IVF. This may be due to the fact that the choice of reproductive material and mechanical fertilization in ICSI contribute to a better quality of embryos compared to those obtained through IVF. In terms of cognitive development, children from the ICSI group demonstrate development similar to their peers conceived spontaneously, subject to comparable perinatal risks. This problem requires further investigation, as there are many factors affecting the cognitive development of children born using reproductive medicine technologies. An important aspect is not only the number of embryo transfers, but also the quality of the embryos used, as well as the overall health of the mother during pregnancy. A deeper analysis of the relationship between the number of fetal transplants and cognitive performance, taking into account the multifactorial nature of the impact of various circumstances, will provide the most complete picture of the impact of ART procedures on the future generation.

Conclusions:

1. Among children conceived using various methods of ART (IVF, ICSI), peculiar variants of the development of higher mental functions were found in comparison with spontaneously conceived peers.

2. Children conceived by IVF, according to our data, have worse indicators of cognitive development and higher risks of dysfunction of neurodynamic parameters (energy factor, cortical structures) of mental activity compared with other groups of children (ICSI, EZ).

3. The type of ART procedure is also important for the subsequent mental development of children conceived with the help of ART; more successful development of children was noted in our sample when using ICSI as an ART procedure.

4. Conducting interdisciplinary research to study the long-term effects of ART procedures on the mental development of children at different ages will help identify the risks of dysfunctional development and create conditions for the timely provision of qualified assistance to the child and his family.

Conclusion. Thus, the variety of statistically significant relationships identified between children conceived by IVF and ICSI indicates specific features of cognitive development depending on the chosen method of fertilization. There is an indirect relationship between the mental development of an artificially conceived child and the number of embryonic transplants performed before pregnancy, as well as the characteristics of embryo transfer, which may cause certain risks of functional insufficiency of certain cognitive functions. Within the framework of the neuropsychological assessment of cognitive development, a clear tendency towards a decrease in general neurodynamics and dynamic indicators of cognitive activity among artificially conceived children in comparison with spontaneously conceived children comes to the fore, the observed functional deficiency of individual components of mental activity has similar manifestations characteristic of perinatal organic pathology. The exposure of children conceived with ART to the greatest risk of dysfunctional cognitive development underscores the need for multidisciplinary research in this field. Creating an integrated interdisciplinary scientific strategy to study the effects of assisted reproduction and other factors on a child's long-term development will help reduce the risk of future dysontogenesis.