In Vitro Fertilization Group Research Articles

Increased Y Chromosome Microdeletions in Cord Blood of Male Newborns From Assisted Reproductive Technology Compared to Natural Conception

ObjectivesTo investigate the incidence of Y chromosome microdeletions in male newborns conceived by intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and natural conception (NC). MethodsA total of 186 male newborns were recruited, including 35 conceived by ICSI, 37 conceived by IVF, and 114 conceived naturally. DNA was extracted from umbilical cord blood after birth. The Yq genetic status of the newborns was determined according to 18 Y-specific sequence tagging sites (STS) markers covering 3 azoospermia factor (AZF) sub-regions and internal control sequences. ResultsPartial AZF microdeletions were identified in 8 of 35 (22.9%) ICSI newborns, 4 of 37 (10.8%) IVF newborns, and 1 of 114 (0.9%) NC newborns. There was a statistically significant difference in the proportion of newborns with partial Y chromosome microdeletions between the ICSI, IVF, and NC groups. When analyzed individually, only the SY114 and SY152 STS markers showed a statistically significant difference in incidence between the 3 cohorts. ConclusionsOur study indicates that the population of male children conceived through assisted reproductive technologies (ART), particularly ICSI, is at an increased risk of genetic defect in the form of partial Y chromosome microdeletions. The growing population of ART-conceived children emphasizes the importance of studying the genetic repercussions of these procedures regarding the future fertility of males conceived in vitro.

Oocyte activation with phospholipase Cζ mRNA induces repetitive intracellular Ca2+ rises and improves the quality of pig embryos after intracytoplasmic sperm injection.

For the intracytoplasmic sperm injection (ICSI) procedure in pigs, an electrical pulse (EP) has been used as an effective method for oocyte stimulation, but unlike sperm, EP is unable to induce Ca2+ oscillations. In this study, we investigated the effects of generating artificial Ca2+ oscillations with phospholipase Cζ (PLCζ) mRNA, a candidate sperm factor, on fertilization, embryonic development, and gene expression after ICSI. Firstly, the concentration of PLCζ mRNA of a fixed volume (1.0 pl) that would induce a pattern of Ca2+ rise similar to that of in vitro fertilized (IVF) sperm was examined and determined to be 300 ng/μl. Secondly, the effects of oocyte stimulation methods on fertilization and embryonic development were investigated. ICSI-oocytes were activated by EP (EP group) or by PLCζ mRNA (PLCζ group). Furthermore, IVF-oocytes (IVF group) and ICSI-oocytes with and without an injection of buffer (buffer and untreated groups, respectively) were used as controls. It was found that the rates of normal fertilization in the PLCζ and EP groups were significantly higher than those in the buffer and untreated groups. The blastocyst formation rates did not differ among the groups. The embryo quality in the EP group was inferior to those in the PLCζ and IVF groups. Additionally, the expression level of a proapoptosis-related gene (Caspase-3) in the EP group was significantly higher than those in the PLCζ and IVF groups. Our data suggest that oocyte activation by PLCζ mRNA has the effect of improving embryo quality.

Efficacy of electro-acupuncture on pregnancy outcomes for women undergoing in vitro fertilization: study protocol for a pilot randomized controlled trial.

In vitro fertilization (IVF) is a technology that assists couples experiencing infertility to conceive children. However, unsuccessful attempts can lead to significant physical and financial strain. Some individuals opt for electro-acupuncture (EA) during IVF, even though there is limited evidence regarding the efficacy of this practice. Thus, this pilot study aims to explore the effectiveness and safety of EA during IVF on pregnancy outcomes. This clinical trial is a parallel, randomized, sham-controlled study. It aims to include a total of 118 infertile women who intend to undergo IVF. The participants will be randomly divided into three groups in a 1:1:1 ratio: the EA + IVF group, the placebo electro-acupuncture (pEA) +IVF group, and the IVF control group. All of the patients will be required to use ovarian stimulation drugs, while those in the EA + IVF and pEA + IVF groups will receive acupuncture treatment at three sessions per week (every other day) until trigger day with a minimum five session. The primary outcome of this trial will focus on the clinical pregnancy rate (CPR). CPR is defined as the rate of achieving clinical pregnancy from the first fresh/frozen embryo transfer cycle with an ultrasound-confirmed gestational sac in the uterine cavity. The secondary outcomes will assess embryology data, biochemical pregnancy rate, early miscarriage rate, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Fertile Quality of Life (FertiQoL), patient retention rate, treatment adherence, and safety outcomes. Ethics approval was obtained from the Ethics Committee of Sichuan Jinxin Xi'nan Women and Children Hospital (number 2021-007). The results will be disseminated through peer-reviewed publications. The participants gave informed consent to participate in the study before taking part in it. https://www.chictr.org.cn, identifier ChiCTR2300074455.

Epigenetic variation in neonatal tissues in infants conceived using capacitation-in vitro maturation vs. in vitro fertilization

ObjectiveTo investigate alterations of the global DNA methylation profile in placenta, cord blood and neonatal buccal smears in infants conceived using in vitro maturation (IVM) with a prematuration step (capacitation-IVM [CAPA-IVM] versus in vitro fertilization (IVF). DesignAnalysis of data from the offspring of participants in a randomized controlled trial. SettingPrivate clinic. PatientsForty-six women with polycystic ovary syndrome and/or high antral follicle count and their offspring (58 newborns). Intervention(s)Women with polycystic ovary syndrome and/or a high antral follicle count participating in the clinical trial were randomized to undergo CAPA-IVM or conventional IVF. Main Outcome Measure(s)At delivery, biological samples including cord blood, placental tissue, and neonatal buccal smear were collected. Genome-wide DNA methylation was determined by Illumina Infinium MethylationEPIC BeadChip. Variability in methylation was also considered and mean variances for the two treatment categories were compared. ResultsIn neonatal buccal smears, there were no significant differences between the CAPA-IVM and conventional IVF groups based on CpG probe after linear regression analysis using a significant cut-off of false discovery rate <0.05 and |Δβ|≥0.05. In cord blood, only one CpG site showed a significant gain of methylation in the CAPA-IVM group. In placenta, CAPA-IVM was significantly associated with changes in methylation at five CpG sites. Significantly more variable DNA methylation was found in five probes in placenta, 54 in cord blood and two in buccal smears after IVM of oocytes. In cord blood samples, 20 CpG sites had more variable methylation in the conventional IVF versus IVM group. Isolated CpG sites showing differences in methylation in cord blood were not associated with changes in gene expression of the overlapping genes. Conclusion(s)CAPA-IVM appeared to be associated with only a small amount of epigenetic variation in cord blood, placental tissue and neonate buccal smears.

The multiple reference range of mean uterine artery pulsatility index for natural and in vitro fertilization singletons during 11-14 gestational weeks.

Ultrasonography of the uterine artery (UtA) in the first and second trimesters of pregnancy can assess uterine-placental blood perfusion and guide early clinical prevention. Establishing normal ranges of the UtA pulsatility index (UtA-PI) at 11-14 weeks of pregnancy is helpful for the early identification of high-risk pregnant women and improving the prognosis. This study aimed to establish a reference range of UtA-PI based on crown-rump length (CRL) for spontaneous and in vitro fertilization (IVF) singleton pregnancy during 11-14 weeks, respectively. A prospective study was performed at Peking Union Medical College Hospital. Healthy, low-risk women with a singleton pregnancy at 11-14 gestational weeks were consecutively recruited for this study from December 2017 to December 2020. All participants underwent routine prenatal ultrasound examination. The CRL of the fetus and the UtA-PI were measured in both uterine arteries, and average values were calculated. The LMS method was used to fit the percentile (P)5, P10, P25, P50, P75, P90, and P95 curves of the UtA-PI value of spontaneous and IVF singleton pregnancy with CRL changes, respectively. A total of 1,962 pregnant women with normal fetuses were included in this study, including 1,792 pregnancies conceived naturally and 170 IVF fetuses. The UtA-PI reference range in the spontaneous pregnancy group was consistently higher than that in the IVF group during 11-14 weeks, and showed a statistically significant difference in UtA-PI for spontaneous and IVF pregnancies (P<0.001). According to the LMS method, each percentile curve of UtA-PI decreased with the increase of CRL in both the natural pregnancy group and the IVF group. The P95 range of UtA-PI for pregnant women with naturally conceived and IVF pregnancy was 2.74 to 2.11 and 2.50 to 1.94, respectively. The overall change of UtA-PI differentials of the two groups showed a downward trend and decreased slightly with the increase of CRL. This study provided a single-center, large sample of data and constructed a CRL-based reference value of UtA-PI for spontaneous and IVF singleton pregnancy, which provides a reliable basis for early UtA evaluation and early clinical decision-making during 11-14 gestational weeks.

Antenatal fetal growth patterns in uncomplicated pregnancies according to mode of conception and placental location

Newborns resulting from in-vitro fertilisation (IVF) had a significantly (P= 0.002) higher birthweight centile than those resulting from spontaneous conception (SC) but no significant changes were found in ultrasound estimated fetal weight (EFW) centile between 20-22 and 32–34 weeks between the IVF and SC groups. When stratified for the IVF methods used, significant (P = 0.02) fastest in-utero fetal growth (mean increase in centile of 5 between 2nd to 3rd trimester) was observed in the frozen embryo transfer (FET) subgroup compared to SC, and to IVF pregnancies resulting from fresh blastocyst transfer (FBT) or from oocyte donation (OD). Low placentation was significantly (P < 0.001) more common in the IVF group than in the SC group but was not associated with a change in growth pattern suggesting that fetal growth in-utero is independent of placental location but may be influenced by embryo freezing.

Infertility and Risk of Autism Spectrum Disorder in Children

Previous studies on the risk of childhood autism spectrum disorder (ASD) following fertility treatment did not account for the infertility itself or the mediating effect of obstetrical and neonatal factors. To assess the association between infertility and its treatments on the risk of ASD and the mediating effect of selected adverse pregnancy outcomes on that association. This was a population-based cohort study in Ontario, Canada. Participants were all singleton and multifetal live births at 24 or more weeks' gestation from 2006 to 2018. Data were analyzed from October 2022 to October 2023. The exposure was mode of conception, namely, (1) unassisted conception, (2) infertility without fertility treatment (ie, subfertility), (3) ovulation induction (OI) or intrauterine insemination (IUI), or (4) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The study outcome was a diagnosis of ASD at age 18 months or older. Cox regression models generated hazard ratios (HR) adjusted for maternal and infant characteristics. Mediation analysis further accounted for the separate effect of (1) preeclampsia, (2) cesarean birth, (3) multifetal pregnancy, (4) preterm birth at less than 37 weeks, and (5) severe neonatal morbidity. A total of 1 370 152 children (703 407 male [51.3%]) were included: 1 185 024 (86.5%) with unassisted conception, 141 180 (10.3%) with parental subfertility, 20 429 (1.5%) following OI or IUI, and 23 519 (1.7%) following IVF or ICSI. Individuals with subfertility or fertility treatment were older and resided in higher-income areas; the mean (SD) age of each group was as follows: 30.1 (5.2) years in the unassisted conception group, 33.3 (4.7) years in the subfertility group, 33.1 (4.4) years in the OI or IUI group, and 35.8 (4.9) years in the IVF or ICSI group. The incidence rate of ASD was 1.93 per 1000 person-years among children in the unassisted conception group. Relative to the latter, the adjusted HR for ASD was 1.20 (95% CI, 1.15-1.25) in the subfertility group, 1.21 (95% CI, 1.09-1.34) following OI or IUI, and 1.16 (95% CI, 1.04-1.28) after IVF or ICSI. Obstetrical and neonatal factors appeared to mediate a sizeable proportion of the aforementioned association between mode of conception and ASD risk. For example, following IVF or ICSI, the proportion mediated by cesarean birth was 29%, multifetal pregnancy was 78%, preterm birth was 50%, and severe neonatal morbidity was 25%. In this cohort study, a slightly higher risk of ASD was observed in children born to individuals with infertility, which appears partly mediated by certain obstetrical and neonatal factors. To optimize child neurodevelopment, strategies should further explore these other factors in individuals with infertility, even among those not receiving fertility treatment.

Взаимосвязь эмоционального состояния и привязанности к плоду у женщин, забеременевших с помощью ЭКО, с перинатальными исходами их детей

Children's development in the early years is significantly linked to further wellbeing. Among many factors involved in early development are mother’s attachment to the fetus and her emotional state during pregnancy. The current study prospectively explores mothers’ characteristics during the third trimester of pregnancy and their newborn children outcomes. The sample included 300 women with natural conception (NC) and 127 women with in-vitro fertilization (IVF), and their newborn children. For mothers, the following instruments were used: the Maternal Fetal Attachment Scale, the Clinical Scale for Self-assessment of Irritability, Depression and Anxiety. For newborns, the following parameters of newborn children outcomes were assessed: gestational period; the length and weight; the Apgar score in the first and fifth minutes after birth. All components of maternal attachment to the fetus were in the normal range for most women in both groups. All aspects of maternal attachment to the fetus were significantly greater in the IVF group. In both groups, more than 35% of women experienced depression and 43% of women experienced moderate/severe levels of anxiety. In the NC group, greater scores on giving of self and enjoying of watching tummy jiggle as the baby kicks inside were associated with less irritation in mothers. In the IVF group, the indicators of women’s attachment to their fetus were not associated with emotional states. Neither mothers’ attachment to their fetus nor their emotional states during pregnancy predicted newborn children outcomes. Children born from IVF had a statistically lower gestational period than in the NC group.

Ribosomal, Telomere, and Mitochondrial Repeat Copy Number Variations in Female Genomes during Ovarian Stimulation and the Prediction of In Vitro Fertilization Outcome: A Pilot Study.

Individual risk assessment of assisted reproductive technologies is essential for personalized treatment strategies. Genetic and genomic indicators of the response to stress by cells could provide individual prognostic indicators for in vitro fertilization (IVF) success. Such indicators include the copy number of ribosomal genes (rDNA), which modulates the level of protein synthesis, and the abundance of mitochondrial DNA (mtDNA), which provides the cell with energy, while the content of telomere repeats (TRs) indicate the biological age. The contents of the three repeats in DNA isolated from blood leukocytes of 40 women before and after ovarian stimulation were assayed prior to IVF. Then, we divided the women into a successful IVF group, IVF+ (N = 17, 7 cases of twins), and a group of failed cases, IVF- (N = 23). The control group included 17 non-pregnant women with natural childbirth in the past. The nonradioactive quantitative hybridization (NQH) method was applied to assay the genome repeat contents. The number of rDNA copies in the IVF+ group was significantly higher than in the IVF- group (p < 10-8). The number of mtDNA copies in the IVF+ group also exceeded those in the IVF- group (p < 0.001), whereas the TR content in the two groups differed, albeit, non-significantly (p < 0.03). Following the ovarian stimulation, the rDNA copy numbers did not change, while the contents of the mtDNA and TR varied significantly. This pilot study has shown that rDNA abundance in blood leukocytes can be considered a stable and effective predictor. Very low numbers of ribosomal repeat copies (<330) entail a high risk of IVF failure. However, a combination of numerous mtDNA and TRs, provided that rDNA content is not very low, increases the probability of multiple pregnancies.

Application of non-invasive prenatal testing to 91,280 spontaneous pregnancies and 3477 pregnancies conceived by in vitro fertilization

BackgroundMany clinical studies based on spontaneous pregnancies (SPs) have demonstrated the superiority of non-invasive prenatal testing (NIPT), and the question of whether this technology is suitable for offspring conceived by assisted reproductive technology has attracted attention. This study aimed to evaluate the application value of NIPT in screening for trisomy (T)21, T18, T13 and sex chromosome aneuploidy (SCA) in pregnant women who conceived by in vitro fertilization (IVF).ResultsIn total, there were 804 high-risk cases [0.88% (804/91280), singleton = 795, twin = 9] in the SP group. Among the 558 invasive prenatal diagnosis (IPD) cases (singleton = 556, twin = 2), 343 (singleton = 342, twin = 1) were true positive, including 213 cases of T21, 28 of T18, 5 of T13 and 97 (singleton = 96, twin = 1) of SCA. The positive predictive values (PPVs) of T21, T18, T13, SCA and T21/T18/T13 combined in singleton pregnancy were 89.12% (213/239), 51.85% (28/54), 21.74% (5/23), 40.00% (96/240), and 77.85% (246/316), respectively, and the PPV of SCA in twin pregnancy was 100.00%. In the IVF group, IPD was performed in 19 (singleton = 16, twin = 3) of the 27 high-risk cases [0.78% (27/3477), singleton = 16, twin = 3], of which 9 (singleton = 8, twin = 1) were true positive, including 5 cases (singleton = 4, twin = 1) of T21 and 4 of SCA. The PPVs of singleton T21, SCA and T21/T18/T13 combined were 66.67% (4/6), 50.00% (4/8) and 57.14% (4/7), respectively, and the PPV of twin T21 was 100.00% (1/1). There were no significant differences in PPV among T21, SCA and T21/T18/T13 combined in singletons between the groups (89.12% vs. 66.67%, p = 0.09; 40.00% vs. 50.00%, p = 0.57; 77.85% vs. 57.14%, p = 0.20). The sensitivity and specificity were higher for singleton and twin pregnancies in the two groups. Based on follow-up results, 1 case of false negative T21 was found in the singleton SP group. Additionally, the mean foetal fraction (FF) of the IVF group was lower than that of the SP group (11.23% vs. 10.51%, p < 0.05).ConclusionNIPT has high sensitivity and specificity in screening chromosomal aneuploidies in both IVF pregnancy and spontaneous pregnancy, so it is an ideal screening method for IVF pregnancy.

How does IVF conception affect pregnancy complications in an older cohort of women, at least 38years of age? Study of a population database.

To compare perinatal outcomes in in-vitro fertilization (IVF) pregnancies versus spontaneous conceptions in woman of advanced maternal age (AMA), and to evaluate the effect of increasing age on IVF pregnancies' outcomes. A retrospective population-based cohort study including pregnant women who delivered between 2008-2014 in the US. First, we included women aged 38-43years and compared those with IVF conceptions (cases) to women with spontaneous conceptions (controls). Thereafter, we compared IVF pregnancies in women aged 38-43years to IVF pregnancies at < 38years of age. Multivariate logistic regression was performed to compare both groups regarding pregnancy,delivery, and neonatal outcomes after adjusting for plausible confounders. Three hundred nine thousand five hundred sixty-seven pregnant women aged 38-43years were identified, with 2,762 composing the IVF group, and 306,805 composing the control group. After adjusting for confounders, the IVF group had a higher risk of several adverse obstetrical outcomes, including hypertensive disorders of pregnancy (aOR 1.31,95%CI 1.06-1.62), gestational diabetes (aOR 1.26,95%CI 1.13-1.41),preterm delivery (aOR 1.45,95%CI 1.16-1.81), cesarean section (CS) (aOR 1.84,95%CI 1.55- 2.19),postpartum hemorrhage (aOR 1.68,95%CI 1.27- 2.24), and maternal infection (aOR 1.90,95%CI 1.31-2.77), with comparable neonatal outcomes. For the second analysis, 9712 IVF pregnancies were included (n = 6950 < 38years, and n = 2762 ≥ 38years). Women ≥ 38years who underwent IVF were more likely to experience hypertensive disorders of pregnancy, CS, hysterectomy and blood transfusion, with comparable neonatal outcomes. IVF AMA pregnancies have a significant increase in myriad perinatal complications compared to spontaneous AMA pregnancies. Younger women undergoing IVF have mildly less complications than their older counterparts.

Pregnancy outcomes and disease phenotype of hypertensive disorders of pregnancy in singleton pregnancies after in vitro fertilization: a retrospective analysis of 1130 cases

BackgroundAlthough in vitro fertilization (IVF) can increase the incidence of hypertensive disorders of pregnancy (HDP), the pregnancy outcomes and disease phenotype of HDP in singleton pregnancies conceived via IVF remain unclear.MethodsThis retrospective cohort study enrolled 1130 singleton pregnancies with HDP from 2016 to 2020. According to the mode of conception, they were allocated into IVF (n = 102) and natural conception (NC) groups (n = 1028). All IVF pregnancies were subdivided into frozen embryo transfer (FET) group (n = 42) and fresh embryo transfer (ET) group (n = 60). Demographic data, pregnancy outcomes and disease phenotypes of HDP among the groups were compared. The risk factors for severe preeclampsia (PE) and early-onset PE were analyzed.ResultsThe incidences of early-onset PE (P<0.001), severe PE (P = 0.016), cesarean section (P<0.001) and preterm births (P = 0.003) in the IVF-HDP group were significantly higher than those in the NC-HDP group, and gestational age at diagnosis of HDP (P = 0.027) and gestational age at delivery (P = 0.004) were earlier and birthweight of the neonates (P = 0.033) were lower in the IVF group. In singleton pregnancies with HDP, IVF was associated with increased risks for both severe PE and early-onset PE (aOR 1.945, 95% CI 1.256, 3.014; and aOR 2.373, 95% CI 1.537, 3.663, respectively), as well as FET, family history of preeclampsia, intrahepatic cholestasis of pregnancy, gestational hypothyroidism and multiparity were associated with increased risks of severe PE and early-onset PE.ConclusionsIn singleton pregnancies with HDP, IVF was associated with an increased incidence of the disease phenotype (severe or early-onset PE), as well as an increased incidence of pregnancy outcomes related to severe PE and early-onset PE.

Effect of vaginal microbiota on pregnancy outcomes of women from Northern China who conceived after IVF.

This study aimed to investigate the correlation between vaginal microbiota and pregnancy outcomes of women who achieved pregnancy via in vitro fertilization (IVF) in Northern China, and to determine a biomarker for evaluation of the risk of preterm births in these women. In total, 19 women from Northern China women who conceived after IVF and 6 women who conceived naturally were recruited in this study. The vaginal samples of the healthy participants were collected throughout pregnancy, that is, during the first, second, and third trimesters. The V3-V4 region of 16S rRNA was used to analyze the vaginal microbiome, and the bioinformatic analysis was performed using QIIME Alpha and Beta diversity analysis. Either IVF group or Natural conception group, bacterial community diversities and total species number of vagnal samples from who delivered at term were significantly higher than those who delivered before term. Low abundance of vaginal bacteria indicates an increased risk of preterm delivery. Further, more abundant vaginal bacteria was found in first trimesters instead of the next two trimesters. Vignal samples collected during first trimester showed richer differences and more predictive value for pregnancy outcoes. In addition, the diversity of the vaginal bacterial community decreased as the gestational age increased, in all samples. Alloscardovia was only found in participants who conceived after IVF, and the percentage of Alloscardovia in viginal samples of normal delivery group is much higher than the samples from preterm delivery group.Vobrio specifically colonized in vagina of pregnant woman in AFT group (those who conceived after IVF (A), first trimester (F), and delivered at term (T)) and Sporosarcina was detected only in women with AFT and AST (those who conceived after IVF (A), second trimester (S), and delivered at term (T)). These data indicates that Alloscardovia, Vobrio and Sporosarcina have great potential in predicting pregnancy outcomes who pregnanted by vitro fertilization. Vaginal microbiota were more stable in women who conceived naturally and those who carried pregnancy to term. Oceanobacillus might act as a positive biomarker, whereas Sulfurospirillum and Propionispira may act as negative biomarkers for the risk of preterm birth.

Retrospective Analysis of the Risk of Breast Carcinoma Following Recurrent In vitro Fertilization Treatments

ABSTRACT Background: Breast cancer is one of the most common cancers affecting women globally, with risk factors including genetic predisposition, environmental influences, and hormonal exposure. The use of in vitro fertilization (IVF) has been associated with high doses of hormonal treatments, raising concerns about the potential increase in breast cancer risk due to these treatments. This study aims to evaluate the incidence of breast carcinoma following recurrent IVF treatments. Methodology: This retrospective cohort study involved 62 women who underwent three or more IVF cycles at a single fertility clinic. Participants were selected based on their comprehensive medical records from the clinic’s database, excluding those with known genetic predispositions to breast cancer. The study cohort was compared with a control group of 62 women who did not undergo IVF but were matched for age and socioeconomic status. Breast cancer incidence was identified through cross-referencing participant records with national cancer registries. Results: Of the 62 women in the IVF group, 8 (12.9%) developed breast carcinoma compared to 4 (6.5%) in the control group. The median time from the first IVF treatment to the cancer diagnosis was 7 years. Statistical analysis using Cox proportional hazards models revealed a hazard ratio of 2.1 for developing breast carcinoma among IVF participants compared to controls, although this was not statistically significant (95% confidence interval: 0.8–5.4; P = 0.12). Conclusion: The findings suggest a higher incidence of breast carcinoma in women undergoing recurrent IVF treatments compared to those who did not undergo such treatments, although the results did not reach statistical significance. The study highlights the need for further research with larger cohorts to robustly determine the relationship between IVF treatments and breast cancer risk. Enhanced screening and monitoring for breast cancer may be advisable for women undergoing repeated IVF cycles.

Should ICSI be implemented on patients with poor-quality embryos in the previous IVF cycle?

This study was to evaluate whether Intracytoplasmic sperm injection (ICSI) can improve the quality of embryo in patients with poor-quality embryos in the previous In-vitro fertilization (IVF) cycle, which was cancelled before transfer. This was a retrospective cohort study of 178 IVF and 158 ICSI cycles for patients with poor-quality embryos in the previous IVF cycle in the Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University from March 2016 to June 2022. The 2 PN rate, oocyte utilization rate , high-quality embryo rate and clinical pregnancy rate were compared between the two groups. Furthermore, the implantation rate, miscarriage rate and cycle cancelation rate were measured and compared. ICSI resulted in a comparable 2 PN rate, oocyte utilization rate and cycle cancelation rate with IVF. The high-quality embryo rate of ICSI group was significantly higher than that of IVF group (5.56% vs. 2.60%, P < 0.05). Eventually, a total of 239 patients performed embryo transfer. ICSI resulted in a significantly higher clinical pregnancy rate (55.56% vs. 40.98%, P < 0.05) compared with IVF, however, there were no notable differences in miscarriage rate and implantation rate. The present study suggested that ICSI significantly improved the high-quality embryo rate and clinical pregnancy of the patients with poor-quality embryos in the previous IVF cycle. Prospective randomized controlled trials are needed to further verify.

Comparison of clinical and preimplantation genetic testing for aneuploidy outcomes between in vitro fertilization and intracytoplasmic sperm injection in sibling mature oocytes from high-risk patients: A retrospective study.

To evaluate the influence of insemination methods on clinical outcomes by assessing preimplantation genetic testing for aneuploidy (PGT-A) outcomes in embryos obtained using in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in sibling mature oocytes from high-risk patients. This retrospective study involved 108 couples with nonmale or mild male factor infertility who underwent split insemination cycles from January 2018 to December 2021. PGT-A was performed using trophectoderm biopsy, array comparative genome hybridization, or next-generation sequencing with 24-chromosome screening. Mature oocytes were divided into IVF (n = 660) and ICSI (n = 1028) groups. The normal fertilization incidence was similar between the groups (81.1% vs. 84.6%). The total number of blastocysts biopsied was significantly higher in the IVF group than in the ICSI group (59.3% vs. 52.6%; p = 0.018). However, euploidy (34.4% vs. 31.9%) and aneuploidy (63.4% vs. 66.2%) rates per biopsy and clinical pregnancy rates (60.0% vs. 58.8%) were similar between the groups. Implantation (45.6% vs. 50.8%) and live birth or ongoing pregnancy (52.0% vs 58.8%) rates were slightly higher in the ICSI group than in the IVF group and miscarriage rate per transfer was slightly higher in the IVF group than in the ICSI group (12.0% vs 5.9%); however no significant difference was observed. IVF and ICSI using sibling mature oocytes had similar clinical outcomes, and euploidy and aneuploidy rates in couples with nonmale and mild male factor infertility. These results suggest that IVF is a useful option, along with ICSI, as an insemination method in PGT-A cycles, especially in high-risk patients.

P-245 Birth of twenty-seven healthy babies following transfer of fresh and frozen-thawed embryos derived from monopronuclear zygotes: a retrospective study

Abstract Study question What are the neonatal outcomes of fresh/frozen-thawed embryos derived from monopronuclear zygotes (1PN)? Is there any influence of the method of fertilization? Summary answer A total of 231 monoembryonic transfers (TF) of fresh or frozen/thawed embryos derived from 1PN zygotes allows to the birth of twenty-seven healthy babies. What is known already Zygotes were classified 16 to 18 hours post insemination according to the extrusion of the second polar body and the number of pronuclei (PN). The «normally fertilized» zygotes display 2 PN and those with 0, 1 or more than 2 PN (&amp;gt; 2PN) are considered as abnormal. If some zygotes are always discarded (&amp;gt;2PN) due to the increased risk of aneuploidy, the transfer of embryos derived from 1PN zygotes remains more controversial. Study design, size, duration Our retrospective study included all conventional in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and frozen embryo transfer (FET) cycles performed between january 2018 and december 2022. Embryo and pregnancy outcomes were analyzed in a first group of 781 fresh cycles (731 patients) and in a second group of 167 FET (150 patients) with embryos derived from 1PN zygote. Only monoembryonic transfers were analyzed for live birth rate (LBR). Participants/materials, setting, methods Only embryos derived from 1PN zygotes were analyzed in our study. For fresh cycles (n = 2762), embryo outcome was analyzed for 1234 (1PN) zygotes (IVF = 648 and ICSI = 586). Fresh embryo TF was performed in 64 cycles. For frozen cycles, TF was achieved in 167 cases. For a total of 231 TF on day 2, 3 or 5, pregnancy and live birth rates were analyzed. Main results and the role of chance At first, 46% of 1PN zygotes from fresh IVF cycles gave rise to embryos of sufficient quality to be transferred or frozen (day 3 or 5/6). This rate decreased to 33% in the fresh ICSI cycles. Blastulation rate was also more important in IVF group (44%) in comparison to ICSI group (20%) without signification (p = 0.1). Fresh TF of 64 patients (32 in each fertilization group) allowed 7 pregnancies in the IVF group (PR = 22%) as compared to 4 pregnancies in the ICSI group (PR = 12%). The 7 IVF pregnancies ended in 4 deliveries of healthy newborns, 2 miscarriages and one pregnancy still ongoing. In the ICSI group, 1 birth of a healthy newborn and 3 miscarriages were observed. Secondary, thirty-six pregnancies were obtained in the 167 FET cycles. A non significative difference was observed between embryos derived from IVF cycles (PR = 26%) and ICSI cycles (PR = 16%) with respectively 15 and 6 healthy babies born. Two pregnancies in each group are still ongoing. Limitations, reasons for caution The main limitation of this study is that it was a retrospective, single-center study with a relatively small number of births. Wider implications of the findings In conclusion, we observed better outcomes in IVF cycles in comparison to ICSI cycles and our center policy to transfer a good quality embryo developed from 1PN zygotes allowed 26 deliveries of 27 healthy newborns during the period analyzed. Trial registration number not applicable

Pregnancy and neonatal outcomes of monozygotic twins resulting from assisted reproductive technology: a 10-year retrospective study

BackgroundMonozygotic twins (MZTs) are associated with high risks of maternal and fetal complications. Even with the widely used elective single embryo transfer (SET), the risk of MZTs following assisted reproductive technology (ART) treatments remains. However, most studies of MZTs focused on the relevant etiology, with few studies describing pregnancy and neonatal outcomes.MethodsThis retrospective cohort study included 19,081 SET cycles resulting from in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT) and testicular sperm aspiration (TESA) performed between January 2010 and July 2020 in a single university-based center. A total of 187 MZTs were included in this investigation. The main outcome measures were the incidence, pregnancy and neonatal outcomes of MZTs. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy loss.ResultsThe overall rate of MZTs from ART treatment in SET cycles was 0.98%. No significant difference was found in the incidence of MZTs among the four groups (p = 0.259). The live birth rate of MZTs in the ICSI group (88.5%) was significantly more favorable than in the IVF, PGT and TESA groups (60.5%, 77.2% and 80%, respectively). IVF resulted in a significantly increased risk of pregnancy loss (39.4%) and early miscarriage (29.5%) in MZT pregnancies compared to ICSI (11.4%, 8.5%), PGT (22.7%, 16.6%) and TESA (20%, 13.3%). The total rate of twin-to-twin transfusion syndrome (TTTS) in MZTs was 2.7% (5/187); however, the TESA group had the highest rate at 20% and was significantly higher than the PGT group (p = 0.005). The four ART groups had no significant effect on the occurrence of congenital abnormalities or other neonatal outcomes in newborns from MZT pregnancies. Multivariate logistic regression analysis revealed that infertility duration, cause of infertility, the total dose of Gn used, history of miscarriages, and the number of miscarriages were not related to the risk of pregnancy loss (p > 0.05).ConclusionsThe rate of MZTs was similar among the four ART groups. The pregnancy loss and the early miscarriage rate of MZTs was increased in IVF patients. Neither the cause of infertility nor the history of miscarriage was correlated with the risk of pregnancy loss. MZTs in the TESA group had a higher risk of TTTS, placental effects influenced by sperm and paternally expressed genes may play a role. However, due to the small total number, studies with larger sample sizes are still needed to validate these result. Pregnancy and neonatal outcomes of MZTs after PGT treatment seem to be reassuring but the duration of the study was short, and long-term follow-up of the children is needed.

Altered local RAS in the liver increased the risk of NAFLD in male mouse offspring produced by in vitro fertilization

BackgroundAssisted reproductive technology (ART) is associated with an increased risk of adverse metabolic health in offspring, and these findings have been demonstrated in animal models without parental infertility issues. However, it is unclear what changes lead to abnormal metabolism. The activation of the renin-angiotensin system (RAS) has been related to various aspects of metabolic syndrome. Thus, we focused on the local RAS of the liver, which is the central organ for glucose and lipid metabolism in offspring conceived by in vitro fertilization (IVF), and studied the role of local liver RAS in metabolic diseases.MethodsMale C57BL/6 mouse offspring obtained by natural pregnancy and IVF were fed a standard chow diet or a high-fat diet (HFD) from 4 weeks of age through 16 weeks of age. We assessed glucose and lipid metabolism, hepatic histopathology, and the gene and protein expression of key RAS components. In addition, the blocker losartan was used from 4 weeks of age through 16 weeks of age to investigate the regulatory mechanisms of abnormal local RAS on metabolic activity in the IVF offspring liver.ResultsThe growth trajectories of IVF offspring body and liver weights were different from those of naturally pregnant offspring. Impaired glucose tolerance (IGT) and insulin resistance (IR) occurred in IVF-conceived male offspring. After continuous HFD feeding, male offspring in the IVF group underwent earlier and more severe IR. Furthermore, there was a trend of lipid accumulation in the livers of chow-fed IVF offspring. Hepatic steatosis was also more serious in the IVF offspring after HFD treatment. Type 1 receptor (AT1R), which is the primary receptor mediating the action of angiotensin (Ang) II, has been confirmed to be upregulated in IVF offspring livers. Losartan reduced or even eliminated most of the significant differences between the IVF and NC groups after HFD consumption.ConclusionsThe upregulation of AT1R expression in the liver increased the activity of the local RAS, resulting in abnormal glucose and lipid metabolism and lipid accumulation in the liver, significantly increasing the risk of nonalcoholic fatty liver disease (NAFLD) in IVF offspring.

Neonatal condition at birth of twins conceived by medically assisted reproductive technology compared to those conceived spontaneously: A retrospective study.

To examine neonatal outcomes at birth among twins conceived spontaneously or by medically assisted reproduction (MAR). A retrospective study was conducted at a single university teaching hospital on data collected between January 1995 and September 2019. Live twin deliveries at more than 24 weeks of pregnancy were included. The study group consisted of women who conceived by MAR and the controls were spontaneously conceived twins. The study group was further divided into two groups: in vitro fertilization (IVF) and ovulation induction (OI) groups. The primary outcomes were umbilical artery pH less than 7.1 and/or Apgar score less than 7 of any twin 5 min after birth. Overall, 2235 eligible twin gestations were included, corresponding to a total of 4470 live neonates; 1009 (45.1%) conceived by MAR (762 [75.5%] IVF and 247 [24.5%] OI) and 1226 (54.9%) conceived spontaneously. Incidence of the primary outcome was 5.3% and 5.1% in the study and control groups, respectively (P = 0.71). The primary outcome was comparable among the IVF (5%), OI (6.2%), and control (5.1%) groups. The results did not change even after adjusting for demographic and obstetric variables, including mode of delivery, which differed between the groups. Neonatal condition of twin pregnancies at birth among MAR subgroups is similar to spontaneously conceived twins.