Assisted Reproductive Technology Methods Research Articles

Assisted reproductive technology and the risk of fetal congenital heart disease: insights from a tertiary-care referral center.

To investigate whether congenital heart diseases exhibit higher rates in pregnancies achieved through assisted reproductive technology (ART) compared to natural conception. In this retrospective cohort study, multinomial logistic regression was employed to analyze the relationship between categories of congenital heart diseases and three conception groups (IVF, ICSI, and natural pregnancies). The main outcome measures are risks of congenital heart disease categories in IVF and ICSI groups using the natural group as reference. We selected fetuses referred for fetal echocardiography to IRCCS Policlinico Sant'Orsola, Bologna, between January 2005 and November 2023, diagnosed with congenital heart diseases. We categorized the congenital heart diseases into six groups based on anatomical and embryological criteria. The estimated risk of left ventricular outflow tract, valvular, conotruncal, and atrioventricular septal defects was lower in the IVF group compared to natural conception. The estimated risk of valvular and atrioventricular septal defects was lower in the ICSI group vs natural. Conversely, the risk for right heart anomalies was higher both in the IVF and ICSI groups compared to natural conception. Heart rhythm diseases were more frequent in IVF pregnancies. When comparing ART methods, valvular defects, conotruncal defects, and right heart anomalies were more frequently observed in the ICSI group, while atrioventricular septal defects were more common in the IVF group. Significant differences were found in the occurrence of congenital heart diseases in pregnancies conceived through IVF and ICSI, versus those conceived naturally, underscoring the importance of further studying the underlying mechanisms of these associations.

P-718 Risk of placenta previa in assisted reproduction: population study with sibling analyses from the committee of Nordic ART and safety

Abstract Study question Which treatment methods and causes of infertility contribute to the increased risk of placenta previa in assisted reproductive technology (ART)? Summary answer Risk was increased across all treatment methods and causes of infertility, but most strongly following fresh blastocyst transfer (fresh-BT) and in women with endometriosis. What is known already A higher risk of placenta previa after ART is well established. Recent studies indicate risk differences according to type of embryo transfer, with particularly high risk seen after fresh-BT. Underlying mechanisms are poorly understood, and maternal factors such as cause of infertility might contribute. Within-mother analyses, where each woman serves as her own control (i.e., sibling design), help disentangle treatment contributions from maternal confounders that are constant between pregnancies. Study design, size, duration The Committee of Nordic ART and Safety (CoNARTaS) cohort consists of linked nationwide data from health registries in four Nordic countries. Data on ART were from Medical Birth Registries (MBRs) and ART quality registries, and data on placenta previa were from MBRs and hospital discharge/specialist health care registries. We included singleton and multiple births after natural conception (NC, n = 5 614 512) and ART (n = 139 694) in Denmark (1994-2014), Finland (1990-2014), Norway (1988-2015) and Sweden (1988-2015). Participants/materials, setting, methods All women who gave their first birth during the study period, at ages 20-45 years, were included, and contributed ≤4 births at 22-44 gestational weeks. We used multilevel logistic regression to compare risk of placenta previa after ART vs NC, both at the population level and within mothers, adjusting for year, maternal age, parity and country. We categorized ART-conception according to embryo cryopreservation, culture duration, and by cause of infertility (any ART method). Main results and the role of chance Population level risk of placenta previa was higher for ART (any method) vs NC (adjusted odds ratio [aOR] 4.16, 95% confidence interval [CI] 3.96-4.37). Controlling for constant maternal factors, the association attenuated, but risk remained higher for ART vs NC (within mothers aOR 2.64, 95% CI 2.31-3.02). Compared to NC, pregnancies from fresh embryos had a higher risk increase (population level aOR 4.69, 95% CI 4.41-4.98; within mothers aOR 3.31, 95% CI 2.81-3.91) than from frozen embryos (population level aOR 2.71, 95% CI 2.35-3.13; within mothers aOR 1.59, 95% CI 1.19-2.13). Further categorization by culture duration showed highest risk increase after fresh-BT (population level aOR 11.51, 95% CI 9.75-13.57; within mothers aOR 7.80, 95% CI 4.59-13.27), and lowest risk increase after frozen cleavage stage embryo transfer (population level aOR 2.33, 95% CI 1.93-2.80; within mothers aOR 1.20, 95% CI 0.83-1.75). Similar results were found across sensitivity analyses, including restriction to singletons. Compared to NC, risk was higher across all causes of infertility, where women with endometriosis and ART-conception had the highest risk increase (aOR 9.35, 95% CI 8.50-10.29), and women with polycystic ovary syndrome who conceived by ART had the lowest risk increase (aOR 1.52, 95% CI 1.12-2.09). Limitations, reasons for caution Analyses within mothers require that women have several births, hence, results might not apply to women with a single birth. Missing data on ART method or cause of infertility made within-mother analyses by cause of infertility unfeasible. We lacked data on extent of placenta previa (low-lying placenta vs placenta previa). Wider implications of the findings Type of embryo transfer and underlying maternal factors, particularly fresh-BT and endometriosis, respectively, both contribute to the increased risk of placenta previa in ART-conceived pregnancies. Identifying the responsible mechanisms might provide opportunities for prevention. Choice of transfer type should incorporate risk of placenta previa as well as other adverse outcomes. Trial registration number NA

P-772 Assisted reproductive technology and the risk of minor congenital heart defects in the newborn

Abstract Study question Are children conceived through assisted reproductive technology (ART) at higher risk of minor congenital heart defects (CHD) compared with naturally conceived (NC) children? Summary answer Contrary to previous studies children conceived through ART had similar risk of minor CHDs compared with children conceived naturally. What is known already Congenital heart defects (CHD) may precipitate cardiac arrhythmias, lead to thromboembolic events, culminate in heart failure or even sudden cardiac demise. A systematic review and meta-analysis showed an elevated odds ratio (OR) for diagnosis of any CHD among children conceived through in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compared with NC children. Other studies indicate that ART is associated with an increased arterial blood pressure and vascular dysfunction in the pulmonary and systemic arterial vasculature. This association persists throughout childhood, adolescence, and early adulthood in individuals conceived through ART; this indicates a lasting impact on the cardiovascular circulatory system. Study design, size, duration The present study is a sub-study to the Copenhagen Baby Heart Study (CBHS), a prospective population-based cohort study of > 25 000 children born in the three main maternity wards in Copenhagen, Denmark, in 2016–2018. Transthoracic echocardiography (TTE) was performed on all children within 60 days of delivery and diagnosis of CHD was reviewed by a specialist in paediatric cardiology. Information regarding parental health, pregnancy, delivery, and the newborn was collected through Danish patient registries. Participants/materials, setting, methods This study includes all children conceived by ART in the CBHS (n = 1 784), and a matched group (1:4 by maternal age at birth) of NC children (n = 7 141). Exclusion criteria were genetic or chromosomal syndromes and heart surgery. Minor CHD was defined as an atrial (ASD) or ventricular septum defects (VSD), bicuspid aortic valve, coarctation of the aorta, pulmonary stenosis, or patent ductus arteriosus. We calculated ORs using logistic regression analyses. Main results and the role of chance The mean maternal age at birth was 34.9 (standard deviation [SD] ±4.4) and 35.1 years (SD ± 4.6) and the newborn mean age at TTE was 12.1 (SD ± 9.3) and 12.2 days (SD ± 9.4) in the ART and NC population, respectively. Parental CHD was registered in 40 (2.2 %) children in the ART group and 121 (1.7 %) in the NC group. Overall, 165 (9.2%) children conceived by ART and 611 (8.6%) NC children were diagnosed with a minor CHD. The most prevalent CHDs were VSD and ASD which accounted for 38.8 % and 35.2 % in children with CHD in the ART group, respectively, and 36.8 % and 33.9 % in children with CHD in the NC group. The unadjusted OR for minor CHD was 1.09 (95% CI 0.91–1.30). Adjustments for maternal age and parental CHD did not change the OR. There were no differences in ORs when stratifying by minor CHD type. We stratified by the method of ART: ICSI and IVF and frozen embryo transfer and fresh embryo transfer, and calculated risk of minor CHD comparing the methods and with NC children. We found no difference in any ORs, crude or adjusted. Limitations, reasons for caution Children born preterm, and children with severe minor and major CHDs, were underrepresented in the cohort indicating parents of such children chose not to participate in a research project that would include another hospital visit. Residual confounding is plausible because parental CHD diagnoses were retrieved from patient registries. Wider implications of the findings The number of children conceived through ART is increasing each year and previous research have found an increased risk of CHD in children conceived through ART. Our findings indicate no increased risk of minor CHD, providing comforting and significant information for advising individuals considering or undergoing ART treatment. Trial registration number NCT02753348

Modern issues of oncofertility and oncoreproduction

The problem of the occurrence of malignant neoplasms in women of reproductive age has not only medical, but also extremely important social significance, as it affects the demographic potential of the country as a whole.The article presents an analysis of the current state of the problem of fertility and preservation of reproductive function in cancer patients. Currently, there are a sufficient number of methods of assisted reproductive technologies aimed at preserving fertility in women with cancer. Among them are the following: cryopreservation of embryos and oocytes, ovarian tissue, in vitro maturation of eggs, obtaining oocytes obtained by removing the ovaries with their subsequent maturation. In addition, auxiliary methods are also distinguished, the main purpose of which is ovarian protection: the use of gonadotropin-releasing hormone agonists, ovarian transposition, gonadal screening. Each method has its advantages and disadvantages. It should be noted that the very fact of the presence of oncological pathology makes its own adjustments to the use of each specific technique. It has been shown that in vitro maturation technology is the most optimal for the preservation and realization of reproductive function in cancer patients. One of its few disadvantages is the high cost and complexity of laboratory control and cultivation of oocytes, which undoubtedly requires highly qualified specialists and relevant experience.

Investigation of the effect of cow estrous serum when added to the maturation medium of oocyte-cumulus complexes <i>IN VITRO</i>

Saving and multiplying the existing livestock population is an important strategic objective that ensures the country's food security and levelling the dependence on imports of genetically valuable highly productive animals. Obtaining farm animal embryos in vitro is one of the methods of assisted reproductive technologies (ART), which can be used both lifetime and post-mortem. This method allows to optimise breeding work with livestock in a short period of time due to the large number of offspring obtained from highly productive individuals. Aim and objectives: to investigate the effect of bovine estrous serum on meiotic oocyte maturation and early embryogenesis prior to blastocyst development, when added to oocyte-cumulus complexes (OCC) maturation medium. A blind randomised controlled trial was conducted on the effect of bovine estral serum on blastocyst development when added to OCC maturation medium. Estral serum was obtained from the blood of clinically healthy cows with pronounced signs of puberty. The study was carried out in conditions of industrial livestock breeding. The material for the study were oocyte-cumulus complexes obtained by the method of lifetime aspiration from 89 Holstein cows with milk productivity of more than 10 thousand kg per lactation. Oocyte-cumulus complexes were divided into 2 groups: Group 1 (control) - oocyte maturation was carried out in commercial IVM medium without addition of estrous serum, Group 2 (experiment) - oocyte maturation was carried out in commercial IVM medium with addition of es trous serum in concentration from 5 to 15%. The hormones, growth factors and biologically active substances contained in estrous serum have no effect on the achievement of OCC at the stage of metaphase II of meiosis, as well as at the stage of fractions; moreover, a negative effect at these stages of development can be traced. However, substances contained in estrous serum are able to saturate and accumulate in OCC at the stage of maturation to metaphase II of meiosis, thus enhancing the potential of oocytes to embryonic development and further positively affect their achievement of the blastocyst stage. The difference in the formation of blastocysts from crushed embryos reaches more than 25%, and the difference in the formation of blastocysts from viable JCCs matured in media without serum and modified with estrous serum is 37.5% in favour of the latter.

Why's it gotta be so complicated: New York's regulation of compensated traditional surrogacy agreements creates a constitutional violation

AbstractNew York's Child–Parent Security Act (CPSA) legalized compensated gestational surrogacy and created a simpler way for parents to establish their parental rights when utilizing assisted reproductive technology (ART). While this was a substantial step forward from past antiquated law, the CPSA continues to heavily regulate compensated genetic, otherwise known as traditional, surrogacy making it challenging to use. The CPSA infringes upon the right to procreate by limiting the ART methods available to those wanting to start a family. This Note proposes an amendment to the current CPSA, including the legalization of compensated traditional surrogacy in New York.

Progesterone in Pregnancy: Evidence-Based Strategies to Reduce Miscarriage and Enhance Assisted Reproductive Technology.

The incidence of miscarriage in early pregnancy, between 5-20 weeks, is common, with a prevalence of between 5-22% of all pregnancies. Miscarriage can have physical, social, and mental health impacts on women and their families. In societies such as Taiwan, where the birth rate is falling and life expectancy is increasing, there is concern that factors that reduce birth rates will have detrimental economic and societal effects. Progesterone has a significant role in maintaining early and successful pregnancy to term. Evidence from preclinical and clinical research on the roles of progesterone has supported recent clinical guidelines in obstetrics and gynecology to reduce rates of early miscarriage and improve methods of assisted reproductive technology (ART). This article aims to present an evidence-based review of current recommendations for the use of progesterone in early pregnancy to reduce miscarriage rates and in luteal phase support for ART, including embryo transfer.

Assessment of developmental rate of mouse embryos yielded from in vitro fertilization of the oocyte with treatment of melatonin and vitamin C simultaneously

BackgroundIn recent decades, in vitro fertilization (IVF) has been widely used as a method of assisted reproductive technology (ART) to improve fertility in individuals. To be more successful in this laboratory method, we used the presence of two common types of antioxidants (melatonin and vitamin C) simultaneously and exclusively in IVF medium.MethodsThe cumulus-oocyte complexes (COCs) were obtained from Gonadotropin-releasing hormone (GnRH) and Human Chorionic Gonadotropin (HMG) -stimulated mice. Subsequently, metaphase II (MII) oocytes were fertilized in vitro. In the experiment, the IVF medium was randomly divided into two equal groups: The control group did not receive any antioxidants. In the treatment group, 100 µM melatonin and 5 mM vitamin C were added to the IVF medium. Finally, oocytes and putative embryos transferred into developmental medium and cultured 120 h after IVF to the blastocyst stage. After and before IVF, oocytes and putative embryos were stained with dichlorodihydrofluorescein diacetate (DCFDA) and the H2O2 level was measured with an inverted fluorescence microscope using ImageJ software. At the end of the fifth day after IVF, the expression of Bax and B cell lymphoma 2 (Bcl2) was evaluated using real-time PCR.ResultsThe levels of reactive oxygen species (ROS) in oocytes and putative embryos observed in the treatment group demonstrated a significant reduce compared to the control group (p ≤ 0.01. (.Furthermore, the number of embryos in the blastocycte stage(P < 0.05), the expression level of the Bcl2 (P < 0.05) gene, the Bax unlike gene, significantly increased compared with the control group.ConclusionWe conclude that the presence of melatonin and vitamin C antioxidants simultaneously and exclusively in the IVF medium leads to a reduction in ROS and ,as a result, improves the growth of the embryo up to the blastocyst stage.

The Impact of Assisted Reproductive Technology on Umbilical Cord Insertion: Increased Risk of Velamentous Cord Insertion in Singleton Pregnancies Conceived through ICSI.

Background and Objectives: Vasa previa (VP) is a significant perinatal complication that can have serious consequences for the fetus/neonate. Velamentous cord insertion (VCI) is a crucial finding in prenatal placental morphology surveillance as it is indicative of comorbid VP. Assisted reproductive technology (ART) has been identified as a risk factor for VCI, so identifying risk factors for VCI in ART could improve VP recognition. This study aims to evaluate the displacement of umbilical cord insertion (CI) from the placental center and to examine the relationship between the modes of conception. Materials and Methods: We conducted a retrospective study at the Obstetrics Department of Osaka Metropolitan University Hospital in Japan between May 2020 and June 2022. The study included a total of 1102 patients who delivered after 22 weeks of gestation. They were divided into three groups: spontaneous pregnancy, conventional in vitro fertilization (cIVF), and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We recorded patient background information, perinatal complications, perinatal outcomes, and a numerical "displacement score", indicating the degree of separation between umbilical CI and the placental center. Results: The displacement score was significantly higher in the cIVF and IVF/ICSI groups compared with the spontaneous conception group. Additionally, the IVF/ICSI group showed a significantly higher displacement score than the cIVF group. Conclusions: Our study provides the first evidence that the methods of ART can affect the location of umbilical CI on the placental surface. Furthermore, we found that IVF/ICSI may contribute to greater displacement of CI from the placental center.

Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection: a Nordic study from the CoNARTaS group

To investigate whether the risk of major congenital malformations is higher in live-born singletons conceived with intracytoplasmic sperm injection (ICSI) compared with invitro fertilization (IVF)? Nordic register-based cohort study. Cross-linked data from Medical Birth Registers and National ART and Patient Registers in Denmark, Norway and Sweden. Data were included from the year the first child conceived using ICSI was born: Sweden, 1992; Denmark, 1994; and Norway, 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden. All live-born singletons conceived using fresh ICSI (n = 32,484); fresh IVF (n = 47,178); without medical assistance (n = 4,804,844); and cryo-ICSI (n = 7,200) during the study period. Different invitro conception methods, and cryopreservation of embryos. Risk of major congenital malformations on the basis of International Classification of Diseases codes. The European Concerted Action on Congenital Anomalies and Twins was used to differentiate between major and minor malformations. Among singletons conceived using fresh ICSI, 6.0% had a major malformation, compared with 5.3% of children conceived using fresh IVF; 4.2% of children conceived without medical assistance; and 4.9% of children conceived using cryo-ICSI; adjusted odds ratio (AOR) 1.07 (95% confidence interval [CI] 1.01-1.14) in ICSI vs. IVF; and AOR 1.28 (95% CI, 1.23-1.35) in ICSI vs. no medical assistance; and AOR 1.11 (95% CI, 0.99-1.26) in ICSI fresh vs. cryo-ICSI. When malformations were grouped by different organ systems, children conceived using ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived using IVF, but there were very few cases in each group. When categorizing children conceived using ICSI according to treatment indication (male factor infertility only vs. other indications), we found a higher risk of hypospadias when ICSI was performed because of male factor infertility only (AOR 1.85 [95% CI 1.03-332]). The indications for ICSI changed over time, as male factor infertility did not remain the primary indication for ICSI throughout the study period. In this large cohort study, we found the risk of major malformations in live-born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing the assisted reproductive technology method for couples without male factor infertility.

Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin.

Sperm chromatin retains small amounts of histones, and chromatin states of sperm mirror gene expression programs of the next generation. However, it remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here, we present a novel mouse model of paternal epigenetic inheritance, in which deposition of Polycomb repressive complex 2 (PRC2) mediated-repressive H3K27me3 is attenuated in the paternal germline. By applying modified methods of assisted reproductive technology using testicular sperm, we rescued infertility of mice missing Polycomb protein SCML2, which regulates germline gene expression by establishing H3K27me3 on bivalent promoters with other active marks H3K4me2/3. We profiled epigenomic states (H3K27me3 and H3K4me3) of testicular sperm and epididymal sperm, demonstrating that the epididymal pattern of the sperm epigenome is already established in testicular sperm and that SCML2 is required for this process. In F1 males of X-linked Scml2-knockout mice, which have a wild-type genotype, gene expression is dysregulated in the male germline during spermiogenesis. These dysregulated genes are targets of SCML2-mediated H3K27me3 in F0 sperm. Further, dysregulation of gene expression was observed in the mutant-derived wild-typeF1 preimplantation embryos. Together, we present functional evidence that the classic epigenetic regulator Polycomb mediates paternal epigenetic inheritance through sperm chromatin.

A Bayesian network model for prediction of low or failed fertilization in assisted reproductive technology based on a large clinical real-world data

Study questionTo construct prediction models based on the Bayesian network (BN) learning method for the probability of fertilization failure (including low fertilization rate [LRF] and total fertilization failure [TFF]) in assisted reproductive technology (ART) treatment.Summary answerA BN model was developed to predict TFF/LFR. The model showed relatively high calibration in external validation, which could facilitate the identification of risk factors for fertilization disorders and improve the efficiency of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.What is known alreadyThe prediction of TFF/LFR is very complex. Although some studies attempted to construct prediction models for TFF/LRF, most of the reported models were based on limited variables and traditional regression-based models, which are unsuitable for analyzing real-world clinical data. Therefore, none of the reported models have been widely used in routine clinical practice. To date, BN modeling analysis is a prominent and increasingly popular machine learning method that is powerful in dealing with dynamic and complex real-world data.Study design, size, durationA retrospective study was performed with 106,640 fresh embryo IVF/ICSI cycles from 2009 to 2019 in one of China's largest reproductive health centers.Participants/materials, setting, methodsA total of 106, 640 cycles were included in this study, including 97,102 controls, 4,339 LFR cases, and 5,199 TFF cases. Twenty-four predictors were initially included, including 13 female-related variables, five male-related variables, and six variables related to IVF/ICSI treatment. BN modeling analysis with tenfold cross-validation was performed to construct the predictive model for TFF/LFR. The receiver operating characteristic (ROC) curves and the corresponding area under the curves (AUCs) were used to evaluate the performance of the BN model.Main results and the role of chanceAll twenty-four predictors were first organized into seven hierarchical layers in a theoretical BN model, according to prior knowledge from previous literature and clinical practice. A machine-learning BN model was generated based on real-world clinical data, containing a total of eighteen predictors, of which the infertility type, ART method, and number of retrieved oocytes directly influence the probabilities of LFR/TFF. The prediction accuracy of the BN model was 91.7%. The AUC of the TFF versus control groups was 0.779 (95% CI: 0.766-0.791), with a sensitivity of 71.2% and specificity of 70.1%; the AUC of of TFF versus LFR groups was 0.807 (95% CI: 0.790-0.824), with a sensitivity of 49.0% and specificity of 99.0%.Limitations, reason for cautionFirst, our study was based on clinical data from a single center, and the results of this study should be further verified by external data. In addition, some critical data (e.g., the detailed IVF laboratory parameters of the sperm and oocytes used for insemination) were not available in this study, which should be given full consideration when further improving the performance of the BN model.Wider implications of the findingsBased on extensive clinical real-world data, we developed a BN model to predict the probabilities of fertilization failures in ART, which provides new clues for clinical decision-making support for clinicians in formulating personalized treatment plans and further improving ART treatment outcomes.Study funding/competing interest(s)Dr. Y. Wang was supported by grants from the Beijing Municipal Science & Technology Commission (Z191100006619086). We declare that there are no conflicts of interest.Trial registration numberN/A.

Agreement on surroggy maternity as a regulator of these legal relations

Thanks to the high level of development of modern medicine, citizens of Ukraine who are faced with the problem of infertility have the opportunity to resort to the help of auxiliary reproductive technologies. In the presence of medical indications, citizens can apply for the services of a surrogate mother. The article considers one of the most interesting methods of assisted reproductive technologies from a legal point of view - surrogate motherhood. Despite the fact that legal grounds for surrogate motherhood appeared in Ukraine back in 2011-2013 (when the relevant normative acts were adopted and entered into force), now there are many practical and theoretical problems related to the institution of surrogate motherhood. At the moment, Ukraine has not adopted a single normative legal act regarding the use of assisted reproductive technologies, however, the current legislation contains a sufficient number of norms regulating this issue. It is worth noting that in Ukraine, a contract of surrogacy can be both commercial and free of charge. The problem of its legal nature is also complicated by the fact that the legislator still did not define the concept of contract, did not foresee the form of conclusion of the contract and its essential conditions. The author points to the presence of visible «gaps» in the current legislation. At the end of the article, the author came to the conclusion about the possibility of eliminating conflicts between the current legislation and the existing judicial practice by adopting a single normative act. The article summarizes national and foreign judicial practice on this issue, and formulates the author's position. It is very important to talk about the need for availability of information regarding the use of assisted reproductive technologies. Therefore, it is important to systematize and organize such information, creating a single regulatory act that regulates the application of such a method of assisted reproductive technologies as surrogacy, as well as to provide a place for a contract on surrogacy .

Особенности течения многоплодной беременности после экстракорпорального оплодотворения

Objective. To study the course of multiple pregnancy after the use of different methods of assisted reproductive technologies. Patients and methods. A total of 234 patients with multiple pregnancy developed through in vitro fertilization (IVF) were examined: 99 patients under the surrogate motherhood program (IVF-SM), 68 women after IVF with donor oocytes (IVF-DO), and 67 patients after IVF with own oocytes (IVF-OO). Patient subgroups were formed based on the presence or absence of obstetric complications. Results. Univariate analysis of pregnancy course showed that the incidence of gestational hypertension was significantly higher in the IVF-DO group than in the IVF-SM and IVF-OO groups. Pre-eclampsia (PE) in patients in the IVF-DO group was significantly more common than in the IVF-SM group (OR: 5.87; 95% CI: 1.94–17.74, p &lt; 0.0005). Intrahepatic cholestasis (11.7%) and gestational diabetes (7.3%) were also more common in the IVF-DO group, but these data were not statistically significant. In multivariate analysis adjusted for maternal age, the incidence of PE remained significantly higher in the IVF-DO group compared with the IVF-SM group (OR: 7.68; 95% CI: 1.64–35.84, p &lt; 0.0055). There were no significant differences between the IVF-DO and IVF-OO groups (OR: 2.8; 95% CI 0.77–10.22, p &lt; 0.1487) and the IVF-OO and IVF-SM groups (OR: 0.36; 95% CI 0.11–1.24, p &lt; 0.1305). Conclusion. Multiple pregnancy following IVF-DO is significantly associated with a higher risk of pre-eclampsia and fetal growth restriction compared with the IVF-OO and IVF-SM groups. Key words: multiple pregnancy, oocyte donation, pre-eclampsia, surrogacy, in vitro fertilization

A Comparison of Oral Dydrogesterone with Vaginal Progesterone for Luteal-Phase Support in In Vitro Fertilization: A Randomized Controlled Trial

Background: The quality of the luteal phase is the most important issue affecting pregnancy outcomes in assisted reproductive technology (ART). Luteal-phase support with the administration of gonadotropin-releasing hormone (GnRH) agonist or progesterone improves the likelihood of pregnancy in ART. Due to disagreements regarding the best pharmaceutical form of progesterone for success of in vitro fertilization (IVF) in ART methods, the present study aimed to compare the clinical efficacy of oral dydrogesterone with vaginal progesterone on the outcome of pregnancy in IVF. Materials and Methods: This unblinded randomized clinical trial was conducted at the Shahid Beheshti Hospital, Obstetrics and Gynecology Centre in Isfahan, Iran, between june 2021 and September 2021. In total, 126 couples were included in the study. All patients underwent controlled ovarian stimulation and IVF. Patients were randomly divided into two groups (n = 63 per group). After embryo transfer, group I was treated with Cyclogest 400 mg twice daily, and group II was treated with oral Duphaston 10 mg twice daily. Results: No significant differences were observed between the two groups in terms of the mean endometrial thickness (P = 0.613), the mean number of transferred embryos (P = 0.100), and the number of implanted embryos (P = 0.338). Additionally, no statistically significant differences in the pregnancy rate were detected between the two groups (P = 0.875). Conclusions: The evidence from this study indicates that Duphaston is as effective as Cyclogest for luteal-phase support.

Reproductive strategies of Russian women: results of the pilot survey

The sphere of reproduction as an integral part of the health of population today is medicalized at all stages of the formation of reproductive decisions — from conception to childbirth. The choice of reproductive strategies is influenced by two polar trends: the increasing importance of innovative methods of assisted reproductive technologies (ART) and medically-associated reproduction (MAR), on the one hand, and the growing popularity of traditional methods of pregnancy and childbirth management based on folk healing, yoga, oriental medicine and health improving practices, homeopathy, popular psychology and so on., on the other. Thus, two sides of procreative behavior manifest themselves: both the patterns reflecting a biomedical approach based on scientific innovations and the social behavioral models related to public perceptions of health, well-being and gender roles in the society. The article presents the results of a pilot survey of women of reproductive age (n=54) conducted in April 2022 via an electronic questionnaire. The study focused on two topics: ART (awareness and attitude to various ART programs) and pregnancy and childbirth (perception of different forms of preparation for childbirth, the preferred form of childbirth, attitude to medical interventions in the birth process). Data analysis showed that women's reproductive intentions remain medicalized and take into account the possibilities of ART. Also, the results of the survey confirm the growing demand for humanization of maternity care, which is reflected in the desire of women to carefully approach organization of their own childbirth and team of assistants, to attend courses for expectant parents, be more informed and comprehensively prepared.

Clinical effectiveness of preconception training in women with sexually transmitted infections after an IVF program

The objective: to prove the clinical effectiveness of preconception preparation of the women with a history of sexually transmitted infections (STIs) after pre-gravid training before assisted reproductive technology (ART) cycles.Materials and methods. 115 women received the suggested pre-gravid training, of which 56 women became pregnant after ART programme and were included in the 1st group and received medical and preventive measures offered by us; 132 women after standard pre-gravid training, of which 55 women became pregnant after ART program and were included in the II group and received generally accepted medical and preventive measures. A clinical analysis of the pregnancy course, childbirth and the condition of newborn children was conducted in 111 women (I and II groups). All patients in the I and II groups had STIs in medical history. Statistical processing of research results was carried out using standard programs “Microsoft Excel 5.0” and “Statistica 8.0”. Results. The rate of threat of pregnancy interruption was significantly lower in the I group – 6 (10.7 %) patients than in the II group – 19 (34.5 %; p&lt;0.001); missed abortion was determined in 3 (5.3 %) cases in the I group versus 6 (10.9%) cases in the II group; spontaneous pregnancy interruption in the I trimester was in 2 (7.1 %) patients in the I group versus 4 (7.3%) women in the II group. Pregnancy was terminated in 5 (8.9 %) pregnant women in the I group and 10 (18.2 %) – in the II group (p&lt;0.05). The threat of late abortion in women in the I group was found significantly less than in patients in the II group – 4 (7.8 %) versus 12 (26. 7%) persons, respectively (p&lt;0.05). Fetal growth retardation (FGR) was diagnosed significantly less in the pregnant women of the I group than in pregnant women of the II group, – 11 (21.6 %) versus 17 (37.8 %) individuals, respectively (p&lt;0.05). The results of cardiotocography (CTG) demonstrated that the satisfactory fetal state was determined in 40 (78.4 %) pregnant women in the I group, which is statistically significantly more than in the II group – 23 (51.1 %; p&lt;0.05) cases.Doubtful non-stress test data were found in the I group more less – 10 (19.6 %) patients versus 15 (33.3 %) cases the II group (p&lt;0.05). Pathological data of CTG were registered in 1 (2.0 %) pregnant women in the I group versus 7 (15.6%) cases in the II group (p&lt;0.05). The risk of fetal distress in the pregnant women in the I group was 13.9 % (95 % CI 7.8-20.0), RR=0.5 (95% CI 0.16-0.66; p=0.002), which confirms the effect of the pre-gravid complex of medical and preventive measures on the fetal distress reducing in the pregnant women of the I group.Premature births were observed significantly less in patients in the I group, than in the II group, which amounted to 6 (11.7 %) versus 12 (26. 7 %) persons (p&lt;0.05). The condition of newborns in the I group was satisfactory in 49 (85.9 %) cases, and the total level of children born with asphyxia in the I group decreased by 2.5 times (p&lt;0.05).Conclusions. Pathogenetically based pre-gravid preparation and therapy proved to be effective for the onset of pregnancy after ART method and positive pregnancy outcomes in 48.6 % of the women; it reduced the reproductive losses by 2 times, the threat of abortion by 3.2 times, the threat of premature birth by 1.6 times, preeclampsia and fetal growth retardation by 1.5 times, and fetal distress during delivery by 2.2 times.

Endometriosis Impact on Fertility: A Review of Pathogenesis, Diagnosis and Treatment

Endometriosis is a common problem affecting 5-10% of women of childbearing age. It is a condition with unknown pathology, leaving us with several theories. However, about half of women with endometriosis complain of difficulty conceiving. The exact mechanism remains unclear. In severe cases, infertility is associated with anatomical disturbances, but the pathophysiology of infertility in mild cases of endometriosis is not understood. From the balance of available evidence, medical treatment of endometriosis does not improve fertility and should not be given to patients wishing to conceive. However, surgical ablation or excision of minimal and mild endometriosis does improve fertility chances. Methods of assisted reproductive technology can be used in combination with hormonal treatment in women with mild endometriosis. Endometriosis treatment is yet to be considered effective. This article is a review of the literature on endometriosis-a disease affecting the quality of life in women all over the globe.

Cryopreservation of embryos: on the question of the concept

The scientific novelty of this study consists in conducting an in-depth comparative legal analysis of the features of the legislative regulation of the essence of the embryo cryopreservation procedure as one of the methods of assisted reproductive technology (using the example of the Republic of Tajikistan and the Russian Federation), as well as formulating the author's own definition of the legal relationship under study. The main methods of this scientific research were the method of comparative analysis (also known as the comparative legal method), as well as the formal legal method. In addition, the methods of scientific cognition of objective legal reality used by the author also include the logical method, system-structural analysis, and the method of legal modeling. The object of this scientific research is the concept and essence of the embryo cryopreservation procedure in accordance with the current legislation of Russia and the Republic of Tajikistan. In turn, the subject of this study was the norms of Russian and Tajik legislation defining the concept and procedure for cryopreservation of embryos, relevant materials of legal practice (statistical data and data from medical websites); scientific works of domestic scientists devoted to the development of the chosen topic. As the main result of this study, the author has developed a proposal on the possible prospective consolidation of the legal definition of the concept of "cryopreservation of embryos" in the provisions of the current legislation of Russia and the Republic of Tajikistan.

PECULIARITIES OF INFERTILITY AND ITS TREATMENT BY ART METHODS IN OLDER REPRODUCTIVE AGE WOMEN

The mother's older reproductive age is an important social and clinical issue. Currently, the proportion of women who postpone childbirth until the end of the 3rd - beginning of the 4th decade of life has increased significantly, especially in Western societies. The success rate of in vitro fertilization (IVF) decreases significantly when women enter the 5th decade of life.&#x0D; The aim of the research: to determine the features of infertility and its treatment by ART methods in women of older reproductive age.&#x0D; Materials. An analysis of 658 patient histories of IVF programs for 2015-2019. Given the purpose and objectives of our research for further analysis, we divided patients into 2 groups: the main group - 333 women aged 35 and over and the control group - 325 women under 35 years. Additionally, in the main group there were 2 subgroups: the first - 199 women aged 35-39 years, the second - 124 women over 40 years.&#x0D; Results. There is a tendency to a gradual increase in the share of older women who want to become mothers: in 2019 the share of women aged 35 and over increased by 6.1% compared to 2015 (from 47.6% to 53.7%), the share of the oldest age group over 40 years is also growing (from 18.3% in 2015 to 21.6% in 2019), and the total share of such patients is quite significant (on average 20.4% in 5 years, which even higher than patients under 30 years of age - 18.5%), which corresponds to the global trend of «delayed motherhood».&#x0D; In recent years, intraplasmic sperm injection (ICSI) has been the most frequently used among ART methods in both the main and control groups: 42.2% in the main group and 47.7% in the control group (p&gt; 0.05), with the share of the oldest women age group was significantly lower than in the control (38.7%, p &lt;0.05). Women in the assisted reproductive technology (ART) programs of the older age group were much more likely to be forced to use oocyte donation (14.2% vs. 3.7% under 35 years of age). After 40 years, this method of ART was used by almost a quarter of patients (23.4%).&#x0D; The analysis revealed a significant discrepancy in the distribution of the etiology of infertility: if in the control the largest share fell on a combination of factors (31.1%) and tubal factor (25.2%), then half (48.0%) of older women are classified in the subgroup «only another female factor», which includes endocrinological disorders, ovarian insufficiency and others. After the age of 35 and 40, the share of women with primary infertility decreases (34.1% and 27.4% against 48.0% under the age of 35) and the share of those who suffer from infertility for more than 5 years increases. Decreased ovarian reserve was diagnosed in 48.0% of patients after 35 years, after 40 years this figure reaches 57.3%, which corresponds to the rates of increase in follicle-stimulating hormone and decrease in anti-mullerian hormone relative to age.&#x0D; A quarter (24.0%) of women over the age of 35 have already had one failed IVF attempt, and 12.6% had 2 or more attempts. After 40 years, the proportion of women with at least two IVF attempts increases to 16.9%.&#x0D; After 35 years, the share of clinical pregnancies per started cycle (30.0% vs. 39.1%) and live births (21.1% vs. 30.2%) significantly decreases. After 40 years, these 2 indicators fall sharply and are 21.8% and 13.7%.&#x0D; Conclusions. Given the increase in the proportion of women who resort to ART in older reproductive age, as well as a number of factors that worsen the prognosis of ART, among which the reduction of ovarian reserve is the least controlled, it is important to find methods to optimize approaches to preparing patients of late reproductive age quality mature oocytes.