Assisted Reproductive Technology Procedures Research Articles

Perinatal Outcomes In Monozygotic Pregnancies Resulting From Assisted Reproductive Technology Procedures: A Single-Center 6-Year Experience Based On A Large Cohort Of Pregnancies.

Monozygotic twin (MZT) pregnancies increase the risk of maternal and infant mortality and include many complications. The present study describes our assisted reproductive technology (ART) procedures from the viewpoint of perinatal outcomes in MZT pregnancies. In this retrospective clinical cross-sectional study, 1159 in vitro fertilization (IVF) cycles performed between October 2014 and December 2019 were reviewed and perinatal outcomes and general clinical conditions analyzed. Sixteen MZT pregnancies were observed, resulting in an incidence of 1.38%. The MZT pregnancy incidence for patients aged ≤35 and >35 years were 0.2% and 1.1%, respectively. Eight MZT pregnancies resulted in live births, while five ended in miscarriage. A significant positive correlation was found between the number of attempts and the age of female (r:0.674; p=0.004) and male (r:0.657; p=0.006) partners. Cumulus-Oocytes Complexes (COC) (r:0.635; p=0.008), Metaphase II Oocyte (MIIO) (r:0.627; p=0.009), Pronucleus Oocyte (PO) (r:0.585; p=0.017) were correlated with serum AMH levels. The number of MZT was positively correlated with male partner age (r:0.527; p=0.036) and negatively correlated with embryo transfer day (ETd) (r:-0.548; p=0.028). The incidence of MZT pregnancies observed in this study was similar to the incidence reported in the literature, although risk was more pronounced among women aged >35 years. Due to potential risks for mothers and fetuses, MZT pregnancies may become a problem as the number of individuals seeking IVF continues to increase.

Maternal metabolic health and fertility: we should not only care about but also for the oocyte!

Metabolic disorders due to obesity and unhealthy lifestyle directly alter the oocyte's microenvironment and impact oocyte quality. Oxidative stress and mitochondrial dysfunction play key roles in the pathogenesis. Acute effects on the fully grown oocytes are evident, but early follicular stages are also sensitive to metabolic stress leading to a long-term impact on follicular cells and oocytes. Improving the preconception health is therefore of capital importance but research in animal models has demonstrated that oocyte quality is not fully recovered. In the in vitro fertilisation clinic, maternal metabolic disorders are linked with disappointing assisted reproductive technology results. Embryos derived from metabolically compromised oocytes exhibit persistently high intracellular stress levels due to weak cellular homeostatic mechanisms. The assisted reproductive technology procedures themselves form an extra burden for these defective embryos. Minimising cellular stress during culture using mitochondrial-targeted therapy could rescue compromised embryos in a bovine model. However, translating such applications to human in vitro fertilisation clinics is not simple. It is crucial to consider the sensitive epigenetic programming during early development. Research in humans and relevant animal models should result in preconception care interventions and in vitro strategies not only aiming at improving fertility but also safeguarding offspring health.

Anaesthesia for assisted reproductive technology (ART): A narrative review

Assisted reproductive technology (ART) is used primarily to address the treatment of infertility which includes medical procedures such as in vitro fertilisation (IVF), intra-cytoplasmic sperm injection (ICSI), gamete intra-fallopian transfer (GIFT) or zygote intra-fallopian transfer (ZIFT). IVF has revolutionised infertility treatment and is nowadays widely accepted all over the world. The IVF is carried out as a daycare procedure and many anaesthetic regimens have been studied, tried and tested so far. An anaesthesiologist's role mainly comes into play during trans- vaginal oocyte retrieval and embryo transfer (ET) process of IVF. Various techniques of anaesthesia are practised which include general or regional anaesthesia, conscious sedation or monitored anaesthesia care, patient-controlled analgesia, acupuncture and transcutaneous electrical nerve stimulation (TENS). The anaesthetic management needs careful consideration of the effect of drugs on the maturation of oocytes or embryonic development, fertilisation and pregnancy rates. In view of the Coronavirus disease-19 (COVID-19) pandemic, ART clinics have been affected and due to the ambiguity of its effects on the reproductive outcome, anaesthesiologists need to be vigilant and cautious with anaesthetic management during pandemic times. This review includes a discussion of various anaesthetic options and agents along with their advantages or disadvantages if any. The literature sources for this review were obtained via PubMed, Medline, Cochrane Library and Google Scholar. The results of 82 out of 110 articles discussing different methods of anaesthesia for ART procedures over 25 years were compiled.

Adjuvant therapy in assisted fertilization procedures

Introduction. Despite continuous advances in assisted reproductive technologies (ART), their outcomes are limited. Before introducing adjuvant therapy to improve the in vitro fertilization (IVF) outcome, it is important to identify appropriate groups of patients, and avoid equal approach for everyone. The objective of this paper was to review the available literature on the most commonly used adjuvant therapy aiming to improve the outcome of IVF. The guidelines of the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine were used, and the available literature was analyzed by searching the Medline ? PubMed and Cochrane databases using appropriate keywords for each entity. Discussion. A review of the literature found no consistent evidence for the standard use of metformin in patients with polycystic ovarian syndrome, nor for use of dehydroepiandrosterone, testosterone, and growth hormone in patients with premature ovarian failure or those with poor response to stimulation. The standard usage of prednisone and aspirin in the general population of patients in ART is also not recommended. Recently, the significance of the oxidative stress has been emphasized, which is why the use of antioxidants in the form of supplementation (melatonin, vitamins C, A, E, coenzyme Q) might be important in improving reproductive outcomes. Conclusion. The modern approach to the problem of infertility has become strictly individual. The application of adjuvant therapy in order to improve the outcome of ART procedures requires an analytical and critical approach in each individual case.

Comparative ejaculatory response, fresh and frozen semen quality and fertility to artificial vagina vs electroejaculation method of semen collection in mithun (Bos frontalis) bulls.

The study aimed to describe a comparative ejaculatory response, fresh and frozen-thawed semen quality and fertility of semen collected by artificial vagina and electroejaculation in mithun. Experimental bulls were divided into two groups, G-I: young bulls (n=4; 4-5years of age) and G-II: older bulls (n=4; 8-10years of age). Sixteen ejaculates were collected from each group G-I (AV1 ) and G-II (AV2 ) by artificial vagina method (control). Thirty-six ejaculates were collected from the same bulls from each group G-I (EE1 ) and G-II (EE2 ) by electroejaculation method (treatment). The study did not reveal any significant (p>0.05) difference in the ejaculatory responses between EE1 and EE2 . Mann-Whitney U test indicated that salivation discomfort sign score was significantly (p<0.05) higher in EE1 . Fresh and frozen-thawed semen quality parameters, and motility and velocity profiles recorded by computer-assisted sperm analyser were significantly (p<0.05) lower in electroejaculation than the artificial vagina. The conception rates (AV1 vs EE1 & AV2 vs EE2 ) at day 35-45 post insemination were nonsignificantly higher (p>0.05) in the artificial vagina group. It concluded that, although artificial vagina method has better semen quality, nevertheless, electroejaculation has the potential for semen collection from free-range mithun bulls to incorporate in assisted reproductive technology procedures.

Genome-Wide Analysis of DNA Methylation in Buccal Cells of Children Conceived through IVF and ICSI.

Early life periconceptional exposures during assisted reproductive technology (ART) procedures could alter the DNA methylation profiles of ART children, notably in imprinted genes and repetitive elements. At the genome scale, DNA methylation differences have been reported in ART conceptions at birth, but it is still unclear if those differences remain at childhood. Here, we performed an epigenome-wide DNA methylation association study using Illumina InfiniumEPIC BeadChip to assess the effects of the mode of conception on the methylome of buccal cells from 7- to 8-year-old children (48 children conceived after ART or naturally (control, CTL)) and according to the embryo culture medium in which they were conceived. We identified 127 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) (FDR < 0.05) with low delta beta differences between the two groups (ART vs. CTL). DMPs were preferentially located inside promoter proximal regions and CpG islands and were mostly hypermethylated with ART. We highlighted that the use of distinct embryo culture medium was not associated with DNA methylation differences in childhood. Overall, we bring additional evidence that children conceived via ART display limited genome-wide DNA methylation variation compared with those conceived naturally.

Pronounced Trace Element Variation in Follicular Fluids of Subfertile Women Undergoing Assisted Reproduction.

Female subfertility is a growing concern, especially in view of an increasing prevalence of polycystic ovary syndrome (PCOS). Assisted reproductive technologies (ART) offer a perspective for pregnancy, but the outcome rate is still suboptimal. The trace elements (TE), copper (Cu), selenium (Se), and zinc (Zn) are essential for fertility and development. We hypothesized that TE concentrations are related to oocyte quality and growth and affect pregnancy outcomes in women undergoing ART. Concentrations of TE were measured by total reflection X-ray fluorescence. Extracellular glutathione peroxidase 3 (GPX3) and selenoprotein P (SELENOP) were determined as additional Se biomarkers. Corresponding serum and follicular fluid (FF) samples were available from women with (n = 20) and without (n = 20) PCOS diagnosis undergoing hormone treatment within the ART procedure, respectively, and FF samples were classified into five groups based on morphological assessment. Serum showed higher TE concentrations than FF, and TE levels correlated positively between both matrices. Individual FF from the same women showed surprisingly high variability in TE concentration, and follicles without oocytes displayed the lowest TE concentrations. Both Se biomarkers GPX3 and SELENOP were present in FF and correlated positively to Se concentrations. Some notable relationships were observed between morphokinetic parameters, TE concentrations, and GPX3 activity. A slightly depressed serum Zn concentration was observed in PCOS. Our results indicate a direct relationship between TE in serum and FF, positive correlations between the three Se biomarkers in FF, and high variability between the FF from the same woman with the lowest TE concentrations in the follicles with the poorest quality. The differences observed in relation to PCOS diagnoses appear relatively minor. Collectively, the data support the notion that TE assessment of follicles may contribute to optimal oocyte selection and subsequently influence ART success.

Current knowledge and the future potential of extracellular vesicles in mammalian reproduction.

Extracellular vesicles (EVs), which contain various functional classes of vesicles, namely exosomes, microvesicles, and apoptotic bodies, represent the major nano-shuttle to transfer bioactive molecules from donor to recipient cells to facilitate cell-to-cell communication in the follicular, oviduct, and uterine microenvironments. In addition to transferring various molecular cargos in the form of miRNAs, mRNAs, proteins, lipids, and DNA molecules, the relative proportion of those molecular cargos in the reproductive fluids can be associated with the physiological and pathological condition of the host animal. Inside the follicle, EV-mediated circulation of miRNAs has been reported to be associated with the growth status of the enclosed oocytes, the metabolic status, and the advanced maternal aging of the animal. Importantly, EVs have the potential to protect their cargo molecules from extracellular degradation or modification while travelling to the recipient cells. This fact together with the enormous availability in almost all biological fluids and spent culture media make them attractive in the search for biomarkers of oocyte/embryo developmental competence, receptive maternal environment and a multitude of reproductive pathophysiological conditions. One of the key factors that have contributed to the lower efficiency of assisted reproductive technologies (ART) is the absence of several maternal in vivo factors in the ART procedures. For this, several studies have been conducted to supplement various components present in the follicular and oviductal fluids into the existing ART procedures and significant positive impacts have been observed in terms of embryo cleavage rate, blastocyst rate, resistance to stress, and survival after cryopreservation. The potential of EVs in shuttling protective messages against environmental and physiological stressors has been evidenced. The effective use of the EV-coupled molecular signals against stress-associated conditions has the potential to pave the path for the application of these protective signals against oxidative stress-associated pathological conditions including PCOS, ageing, and endometritis. In this review, we provide current knowledge and potential future use of EVs as remedies in reproductive pathophysiological conditions, mainly in follicular and oviductal microenvironments.

Cryopreservation of Gametes and Embryos and Their Molecular Changes.

The process of freezing cells or tissues and depositing them in liquid nitrogen at –196 °C is called cryopreservation. Sub-zero temperature is not a physiological condition for cells and water ice crystals represent the main problem since they induce cell death, principally in large cells like oocytes, which have a meiotic spindle that degenerates during this process. Significantly, cryopreservation represents an option for fertility preservation in patients who develop gonadal failure for any condition and those who want to freeze their germ cells for later use. The possibility of freezing sperm, oocytes, and embryos has been available for a long time, and in 1983 the first birth with thawed oocytes was achieved. From the mid-2000s forward, the use of egg vitrification through intracytoplasmic sperm injection has improved pregnancy rates. Births using assisted reproductive technologies (ART) have some adverse conditions and events. These risks could be associated with ART procedures or related to infertility. Cryopreservation generates changes in the epigenome of gametes and embryos, given that ART occurs when the epigenome is most vulnerable. Furthermore, cryoprotective agents induce alterations in the integrity of germ cells and embryos. Notably, cryopreservation extensively affects cell viability, generates proteomic profile changes, compromises crucial cellular functions, and alters sperm motility. This technique has been widely employed since the 1980s and there is a lack of knowledge about molecular changes. The emerging view is that molecular changes are associated with cryopreservation, affecting metabolism, cytoarchitecture, calcium homeostasis, epigenetic state, and cell survival, which compromise the fertilization in ART.

International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014†.

International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014†.

Дисморфизмы ооцитов в программах ВРТ: Обзор литературы

Актуальность: Вспомогательные репродуктивные технологии (ВРТ) интенсивно развиваются и в последние десятилетия ​​приобретают все большее значение вследствие растущего количества бесплодных пар во всем мире. Основным объектом, используемым в процедурах ВРТ, являются ооциты человека. Следовательно, качество ооцитов может быть определяющим фактором основных ключевых показателей ВРТ.&#x0D; Цель данного обзора: провести анализ литературы и результатов исследований в области ВРТ по изучению экстрацитоплазматических дисморфизмов ооцитов человека – морфологических изменений вне цитоплазматической структуры ооцитов, их влияния на оплодотворение, дробление, частоту имплантации, частоту клинической беременности, а также возможность их использования в качестве биомаркеров для прогнозирования качества эмбрионов, бластоцист и их дальнейшего имплантационного потенциала.&#x0D; Материалы и Методы: Для написания данного обзора был осуществлен поиск отечественных и зарубежных публикаций в российских и международных системах поиска (PubMed, eLibrary) за 2000-2020 годы по ключевым словам «бесплодие», «ЭКО», «ооцит», «морфологическая оценка ооцитов», «дисморфизмы ооцитов», «вспомогательные репродуктивные технологии».&#x0D; Результаты: В обзоре представлены данные литературы и анализ результатов исследований в области ВРТ, посвященных изучению морфологических особенностей и аномалий (дисморфизмов) ооцитов человека. Описаны виды экстрацитоплазматических аномалий ооцитов, встречающихся в клинической практике экстракорпорального оплодотворения, их влияние на оплодотворение, дробление, частоту имплантации, частоту клинической беременности, а также возможность их использования в качестве биомаркеров с целью прогнозирования качества эмбрионов и бластоцист, их дальнейшего имплантационного потенциала.&#x0D; Выводы: При проведении программ ВРТ качество ооцитов должно оцениваться в комплексе и включать в себя оценку полученных ОКК на ТВП, оценку наличия дисморфизмов в ооцитах при проведении оплодотворения, оценки эмбрионов в процессе дробления, качество получаемых бластоцист, анализ показателей частоты имплантации, частоты клинической беременности и живорождения в сочетании с рядом других современных методов исследования.

Imaging of complications following treatment with assisted reproductive technology: keep on your radar at each step.

Since the advent of assisted reproductive technology(ART), the utilization of ART procedures has become increasingly popular among women seeking to establish pregnancy. Radiologists are therefore likely to encounter the various complications of ART therapy. The most common is ovarian hyperstimulation syndrome; others are multiple, ectopic, and heterotopic pregnancies. Ultrasonography is considered the initial modality to investigate ART complications, However, nonspecific symptoms might need the use of an additional imaging modality, such as computed tomography or magnetic resonance imaging, as a problem-solving tool. This article briefly discusses the steps involved in assisted reproduction. Its aim is to help radiologists become familiarized with the multimodality imaging features of the spectrum of ART-related complications. Their key imaging features and differential considerations are emphasized. This will facilitate the provision of precise and timely diagnoses, and aid the avoidance of fatal consequences.

ASSISTED REPRODUCTIVE TECHNOLOGY PROCEDURES IN THE US PRIOR TO AND DURING THE COVID-19 PANDEMIC

The COVID-19 pandemic has created many uncertainties for those pursuing fertility care and assisted reproductive technology (ART) procedures, due to ever-changing healthcare restrictions. There is a lack of research on large-scale data for ART procedures during the pandemic. The objective of our study is to evaluate ART procedures, specifically oocyte retrieval and in vitro fertilization (IVF) cycles, prior to and during the pandemic.

The impact of medical therapies and factors related to treatment procedures in women with rheumatoid arthritis and inflammatory bowel disease receiving assisted reproduction: a nationwide cohort study

To examine whether medications used to treat rheumatoid arthritis (RA)/chronic inflammatory bowel disease (IBD), or factors related to the assisted reproductive technology (ART) procedures, impact the success of ART. In women with RA/IBD, initial studies have shown a reduced chance of a live-born child after ART. Cohort study. Nationwide Danish health registries. All Danish women with a fresh embryo transfer from January 1, 2006, through 2018. The cohorts comprised 1,824 embryo transfers in women with RA/IBD and 97,191 embryo transfers in women without RA/IBD. Observational, noninterventional study. Live birth per fresh embryo transfer. The chance of a live birth in women with RA/IBD receiving ART, compared with other women receiving ART, had an adjusted odds ratio (OR) of 0.79 (95% confidence interval [CI], 0.68-0.91). Prescribed corticosteroids before embryo transfer were positively associated with a live-born child (adjusted OR, 1.21; 95% CI, 1.12-1.31), while the use of antiinflammatory/immunosuppressive agents did not have significant importance. Intracytoplasmic sperm injection was associated with a reduced chance (adjusted OR, 0.94; 95% CI, 0.90-0.97). Type of hormone treatment protocol did not have significant importance, and transfer at the blastocyst stage was positively associated with a live-born child (adjusted OR, 1.54; 95% CI, 1.46-1.62). In women with RA and/or IBD, prescribed corticosteroid before embryo transfer and embryo transfer at the blastocyst stage were associated with successful ART. Intracytoplasmic sperm injection was associated with a slightly reduced chance. Antiinflammatory/immunosuppressive agents and type of hormone protocols did not have significant importance.

Financing future fertility: Women's views on funding egg freezing.

Like other assisted reproductive technology (ART) procedures, the cost of egg freezing (EF) is significant, presenting a potential barrier to access. Given recent technological advancements and rising demand for EF, it is timely to reassess how EF is funded. An online cross-sectional survey was conducted in Victoria, Australia and was completed by 656 female individuals. Participants were asked their views on funding for both medical and non-medical EF. The median age of participants was 28 years (interquartile range 23–37 years) and most participants were employed (44% full-time, 28% part-time, 33% students). There was very high support for public funding for medical EF (n = 574, 87%), with 302 (46%) participants indicating support for the complete funding of medical EF through the public system. Views about funding for non-medical EF were more divided; 43 (6%) participants supported full public funding, 235 (36%) supported partial public funding, 150 (23%) supported coverage through private health insurance, and 204 (31%) indicated that non-medical EF should be self-funded. If faced with the decision of what to do with surplus eggs, a high proportion of participants indicated that they would consider donation (71% to research, 59% to a known recipient, 52% to a donor programme), indicating that eggs surplus to requirements could be a potential source of donor eggs. This study provides insights that could inform policy review, and suggests revisiting whether the medical/non-medical distinction is a fair criterion to allocate funding to ART.

A Comparative Study to Assess the Efficacy of Two Different Estradiol Formulations during In Vitro Fertilization.

Improvements in stimulation protocols, introduction of vitrification, and changes in clinical practices have contributed to improved efficacy and safety of assisted reproductive technology (ART) procedures. This has also led to a concomitant increase in number of cycles requiring hormone replacement therapy (HRT) protocol for performing an embryo transfer. Successful implantation is dependent on endometrial thickness which in turn is regulated by temporal regulation of hormones. Careful control of estrogen levels determines uterine receptivity. One of the most used drugs for achieving appropriate endometrial lining of >7 mm in HRT is estradiol valerate. Although different estrogen formulations with varying physicochemical properties exist, there is not enough literature to support if the differences translate into a discernible clinical outcome in an in vitro fertilization (IVF) setting. Objective and Method. In this study, retrospective in nature, we compare the efficacy of oral estradiol hemihydrate with estradiol valerate in HRT cycles in 2,529 Indian women, undergoing treatment at a center in India between Jan 2017 and May 2019. Results. Our results primarily indicate that between the estradiol valerate and estradiol hemihydrate treatment groups, the implantation rate (IR) was 47.42% and 49.07%, respectively (P value 0.284), and the endometrial thickness (mean ± SEM in mm) that was achieved was 9.25 ± 0.038 mm and 9.57 ± 0.058 mm (P value < 0.001), respectively. There were no significant differences observed in the secondary outcome measures including clinical pregnancy rate, abortion rate, ectopic pregnancy, and live birth rate. Conclusions. Hence, this study concludes that oral estradiol hemihydrate and estradiol valerate are therapeutically equivalent and provide similar clinical outcomes in an IVF setting.

D-chiro-inositol, Vitamin D, and Epigallocatechin Gallate Avoid Surgery in Females with Uterine Fibroids: Two Case Reports

Uterine fibroids (UF) represent the most common benign tumours in females of reproductive age, and can negatively affect fertility. Patients with UFs need to reduce the tumour size with pharmacological treatments or surgically remove the fibroid before using assisted reproductive technology (ART). On the other hand, surgery implies long waiting times before ART to avoid the risk of rupture of the uterus. Long waiting periods are often unacceptable for older individuals who want to undergo ART procedures. Unfortunately, no specific and safe treatment for UFs is currently available. Here the author reports two cases of patients with UFs and associated heavy menstrual bleeding who seek pregnancy through ART. Both underwent a daily treatment with epigallocatechin gallate, vitamin D, vitamin B6, and D-chiro-inositol for 3 months. The patients showed a volume reduction of 73.8% and 68.4%, respectively. This was associated with decreased blood loss (42.1% and 48.7%, respectively). After 3 months from the end of the treatment, both patients underwent ART procedure without the need for surgical intervention.

P–380 Differential concentrations of maternal and fetal hemopexin and α1-microglobulin in preeclampsia from IVF pregnancies depending on the presence of corpus luteum at embryo transfer

Abstract Study question Does the presence of corpus luteum (CL) in in vitro fertilization (IVF) treatments affect maternal and fetal concentrations of hemopexin and α1-microglobulin in preeclampsia? Summary answer Decreased hemopexin and increased α1-microglobulin levels in maternal and fetal blood in IVF pregnancies with absence of CL particularly in pregnancies complicated by preeclampsia. What is known already: Pregnancies after frozen embryo transfer (FET) in programmed cycles have higher rates of hypertensive disorders of pregnancy, suggesting a link between the absence of CL in programmed cycles and adverse maternal outcomes.Cardiovascular function is impaired early in pregnancy in women conceiving by IVF treatments in the absence of CL.Plasma relaxin–2, a potent vasodilator and stimulus of decidualization, has been reported to be undetectable in a non-CL cohort, but markedly elevated in a multiple-CL cohort through pregnancy.Hemopexin and α1-microglobulin act as scavengers that eliminate free heme-groups responsible for hemoglobin-induced oxidative stress known to contribute to preeclampsia development. Study design, size, duration A case-control study of 160 singleton pregnancies recruited from 2016 to 2020, including 54 spontaneous pregnancies from fertile couples, 50 conceived by IVF following fresh embryo transfer (ET) and FET in natural cycle (presence of CL) and 56 IVF after fresh oocyte-donation or FET in programmed cycles (absence of CL). Pregnancies were subclassified according to the presence of preeclampsia in uncomplicated, preeclampsia and severe preeclampsia cases. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. Spontaneous pregnancies from fertile couples were randomly selected from our general population and matched to IVF by gestational age at birth. Hemopexin and α1-microglobulin concentrations were measured by ELISA in maternal and cord plasma collected at delivery. All comparisons were adjusted for age, ethnicity, prematurity, birthweight centile, oocyte-donation and FET cycles. Main results and the role of chance Parental ethnicity, body mass index, exposure to aspirin and corticoids during pregnancy, mean gestational age at birth and birthweight were similar in all study groups. While maternal hemopexin levels were lower in treatments without CL, the IVF group with one or several CL showed significantly increased hemopexin concentrations, both in uncomplicated and preeclampsia cases (uncomplicated: spontaneous conceptions median 1520 ug/ml [interquartile range 1054–1746], IVF with CL 1554 [1315–1778], IVF without CL 1401 [1130–1750]; Preeclampsia: spontaneous conceptions 1362 [1121–1667], IVF with CL 1372 [403–2558], IVF without CL 1215 [971–1498]). Maternal α1-microglobulin was significantly higher in the absence of CL in severe preeclamptic cases as compared to spontaneous pregnancies and IVF with CL (spontaneous conceptions median 23 ug/ml [interquantile range 20–24], IVF with CL 24 [24–26], IVF without CL 26 [25–28]). The cord blood profiles were identical to the maternal for both biomarkers. Overall, and in line with previous studies, preeclamptic pregnancies independently of the mode of conception, showed decreased concentrations of hemopexin and increased concentrations of α1-microglobulin both in maternal and fetal plasma, with more pronounced changes in severe preeclampsia cases. Limitations, reasons for caution Infertility factors contribution to the outcome cannot be unraveled from the assisted reproductive technologies procedure itself as we have only included spontaneous pregnancies from fertile couples. Adjustments for oocyte-donation and FET modalities were performed due to the higher proportion of these features in the ET in programmed cycles group. Wider implications of the findings: These findings acknowledge physiological differences between pregnancies following ET in stimulated and natural versus programmed cycles, supporting the hypothesis that the CL activity could influence perinatal results. This approach to perinatal outcomes in IVF patients could lead to changes in ET protocols in order to develop a CL if possible. Trial registration number Not applicable

P–766 Neurodevelopment in fetuses conceived by assisted reproductive technologies following fresh and frozen embryo transfer

Abstract Study question Do in vitro fertilization (IVF) offspring present different neurodevelopment assessed by fetal neurosonography and infant neurobehavioral tests as compared to those spontaneously conceived (SC)? Summary answer IVF offspring, especially those obtained after fresh embryo-transfer (ET), showed subtle structural differences in fetal neurosonography and poorer neurobehavioral scores at twelve months of age. What is known already The number of pregnancies following assisted reproductive technologies (ART) is currently increasing worldwide. Concerns about the neurodevelopment of subjects conceived by IVF have been rising and mostly studied in children and adolescents with inconsistent results. Many of the identified risk associations were only observed in subgroups or disappeared after adjustment for covariates, mainly multiple pregnancy and gestational age at birth. It is unknown whether fetal brain development and cortical folding differ prenatally in IVF fetuses as compared to SC. Study design, size, duration This is the first study examining fetal neurodevelopment by neurosonography in IVF fetuses. A prospective cohort study of 210 singleton pregnancies recruited from 2017 to 2020, including 70 SC gestations, 70 conceived by IVF following frozen ET (FET) and 70 IVF after fresh ET. Fetal neurosonography was performed in all pregnancies. Additionally, Ages &amp; Stages Questionnaires (ASQ) were obtained at 12 months of corrected age. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. SC pregnancies were randomly selected from low-risk fertile couples and paired to IVF by maternal age. Fetal neurosonography including transvaginal approach was performed at 32±2 weeks of gestation, measured off-line by a single investigator and normalized by biparietal or occipitofrontal diameter. ASQ were obtained postnatally, at 12 months of corrected age. Main results and the role of chance Study groups were similar and comparable regarding maternal age, body mass index, study level and employment rate together with exposure to smoke, alcohol, aspirin and corticoids during pregnancy, gestational age (32±2 weeks) and estimated fetal weight (1700±400g) at neurosonography. As compared to SC pregnancies, both IVF populations showed differences in cortical development with reduced parieto-occipital (fresh ET 12.5mm [SD 2.5] vs FET 13.4 [2.6] vs SC 13.4 [2.6]), cingulate (fresh ET 5.8 [IQR 4.2–7.4] vs FET 5.8 [4.1–7.5] vs SC 6.5 [4.8–7.8]) and calcarine (fresh ET 13.5 [IQR 10.1–16.1] vs FET 14.5 [12.1–15.8] vs SC 16.4 [14.3–17.9]) sulci depth together with lower Sylvian fissure grading. Cortical development changes were more pronounced in the fresh ET group as compared to FET. Corpus callosum length and insula depth were lower in FET and fresh ET groups, respectively. Neurosonographic changes remained statistically significant after adjustment by ethnicity, gender, gestational age and weight centile at scan. IVF infants showed worse ASQ scores, especially in fresh ET for communication, personal-social, fine-motor and problem-solving skills. Gross-motor scores were significantly lower in FET as compared to SC and fresh ET. Differences were statistically significant after adjustment by maternal ethnicity, study level, employment status, breastfeeding, gender and corrected age. Limitations, reasons for caution The reported neurodevelopmental differences are subtle, with most neurosonographic findings lying within normal ranges. Infertility factors contribution to the outcome cannot be unraveled from the ART procedure itself. The milder features found in FET individuals cannot condition the techniqués choice and must be considered together with their global perinatal results. Wider implications of the findings: Neurosonography is an appropriate tool to identify subtle brain differences between fetuses exposed and not exposed to ART. Prenatal features were consistent with postnatal neurobehavioral findings. These results support the relevance of a neurodevelopmental follow-up in IVF patients. Further studies are warranted to assess the long-term performance in these subjects. Trial registration number Not applicable

P-766 Neurodevelopment in fetuses conceived by assisted reproductive technologies following fresh and frozen embryo transfer

Abstract Study question Do in vitro fertilization (IVF) offspring present different neurodevelopment assessed by fetal neurosonography and infant neurobehavioral tests as compared to those spontaneously conceived (SC)? Summary answer IVF offspring, especially those obtained after fresh embryo-transfer (ET), showed subtle structural differences in fetal neurosonography and poorer neurobehavioral scores at twelve months of age. What is known already The number of pregnancies following assisted reproductive technologies (ART) is currently increasing worldwide. Concerns about the neurodevelopment of subjects conceived by IVF have been rising and mostly studied in children and adolescents with inconsistent results. Many of the identified risk associations were only observed in subgroups or disappeared after adjustment for covariates, mainly multiple pregnancy and gestational age at birth. It is unknown whether fetal brain development and cortical folding differ prenatally in IVF fetuses as compared to SC. Study design, size, duration This is the first study examining fetal neurodevelopment by neurosonography in IVF fetuses. A prospective cohort study of 210 singleton pregnancies recruited from 2017 to 2020, including 70 SC gestations, 70 conceived by IVF following frozen ET (FET) and 70 IVF after fresh ET. Fetal neurosonography was performed in all pregnancies. Additionally, Ages &amp; Stages Questionnaires (ASQ) were obtained at 12 months of corrected age. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. SC pregnancies were randomly selected from low-risk fertile couples and paired to IVF by maternal age. Fetal neurosonography including transvaginal approach was performed at 32±2 weeks of gestation, measured off-line by a single investigator and normalized by biparietal or occipitofrontal diameter. ASQ were obtained postnatally, at 12 months of corrected age. Main results and the role of chance Study groups were similar and comparable regarding maternal age, body mass index, study level and employment rate together with exposure to smoke, alcohol, aspirin and corticoids during pregnancy, gestational age (32±2 weeks) and estimated fetal weight (1700±400g) at neurosonography. As compared to SC pregnancies, both IVF populations showed differences in cortical development with reduced parieto-occipital (fresh ET 12.5mm [SD 2.5] vs FET 13.4 [2.6] vs SC 13.4 [2.6]), cingulate (fresh ET 5.8 [IQR 4.2-7.4] vs FET 5.8 [4.1-7.5] vs SC 6.5 [4.8-7.8]) and calcarine (fresh ET 13.5 [IQR 10.1-16.1] vs FET 14.5 [12.1-15.8] vs SC 16.4 [14.3-17.9]) sulci depth together with lower Sylvian fissure grading. Cortical development changes were more pronounced in the fresh ET group as compared to FET. Corpus callosum length and insula depth were lower in FET and fresh ET groups, respectively. Neurosonographic changes remained statistically significant after adjustment by ethnicity, gender, gestational age and weight centile at scan. IVF infants showed worse ASQ scores, especially in fresh ET for communication, personal-social, fine-motor and problem-solving skills. Gross-motor scores were significantly lower in FET as compared to SC and fresh ET. Differences were statistically significant after adjustment by maternal ethnicity, study level, employment status, breastfeeding, gender and corrected age. Limitations, reasons for caution The reported neurodevelopmental differences are subtle, with most neurosonographic findings lying within normal ranges. Infertility factors contribution to the outcome cannot be unraveled from the ART procedure itself. The milder features found in FET individuals cannot condition the techniqués choice and must be considered together with their global perinatal results. Wider implications of the findings Neurosonography is an appropriate tool to identify subtle brain differences between fetuses exposed and not exposed to ART. Prenatal features were consistent with postnatal neurobehavioral findings. These results support the relevance of a neurodevelopmental follow-up in IVF patients. Further studies are warranted to assess the long-term performance in these subjects. Trial registration number not applicable