In Vitro Fertilization-embryo Transfer Research Articles

Trace elements exposure affects the outcomes of in vitro fertilization embryo transfer, a cohort study in Northern China.

With urbanization and industrialization process accelerated, humans are exposed more and more trace elements. This study aimed to explore the potential associations of trace elements with the outcomes of in vitro fertilization embryo transfer (IVF-ET). Total 181 women who underwent IVF-ET were enrolled, among which 89 women underwent fresh ET after IVF. Trace elements were measured in the serum and follicular fluid (FF) samples by inductively coupled plasma-mass spectroscopy. The associations of the levels of different trace elements with IVF-ET outcomes, including normal fertilization, high-quality embryos, and clinical pregnancy (fresh ET) were analyzed. Twenty-five out of twenty-eight trace elements showed higher concentrations in the serum than those in the FF. Normal fertilization was positively associated with Cu and Mn in the FF. High-quality embryos was positively associated with Cu in the serum and FF, and Zn in the serum. Clinical pregnancy was positively associated with Ge in the serum, and inversely associated with Al, Ba, and Pb in the serum. Additionally, poor outcomes of IVF-ET should be noticed in women with FF level of Cu < 955.38ng/mL, FF level of Mn < 3.42ng/mL, serum level of Ge < 6.11ng/mL, serum level of Al > 28.44ng/mL, and serum level of Pb > 0.90ng/mL. IVF-ET outcomes were positively associated with Cu, Mn, Zn, and Ge, and inversely associated with Al and Pb. Properly controlling the exposure of relevant trace elements is necessary for patients with the need of IVF-ET.

The actor-partner interdependence model of fertility stress and marital quality among couples undergoing in vitro fertilization and embryo transfer: The mediating role of dyadic coping.

To explore the relationships among fertility stress, dyadic coping and marital quality in couples undergoing in vitro fertilization-embryo transfer (IVF-ET). Couples receiving IVF-ET treatment at the clinic of the reproductive medicine centre of a hospital in China from February 2023 to October 2023 were selected by convenience sampling. A general information questionnaire, the Infertility Fertility Stress Scale (COMP-FPSS-SF), the dyadic coping inventory, and the marital adjustment test were used to evaluate the results. AMOS24.0 software was used to construct an actor-partner interdependence model that extended to mediation to analyze the relationships among couples' fertility stress, dyadic coping, and marital quality. The fertility stress level of IVF-ET wives was significantly higher than that of their husbands (p<0.05). Wives' levels of dyadic coping and marital quality were significantly lower than those of husbands (p<0.05). Fertility stress, dyadic coping, and marital quality were positively correlated between IVF-ET couples (p<0.01). In terms of the actor effect, the fertility stress of IVF-ET couples had a significant impact on their marital quality through their dyadic coping (β=-0.188, p<0.05; β=-0.109, p<0.05). In terms of partner effects, wives' fertility stress significantly affected their husbands' marital quality through their own or their husbands' dyadic coping (β=-0.055, p<0.01; β=0.157, p<0.01). Dyadic coping mediates the relationship between fertility stress and marital quality in IVF-ET couples. Nurses can use husbands and wives as central individuals and dyadic coping as the starting point to formulate intervention measures to reduce fertility stress and improve marital quality.

Tuberculosis in infertility and in vitro fertilization-embryo transfer.

Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

Effects of ovarian stimulation on embryo euploidy: an analysis of 12874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders.

Does ovarian stimulation and the ovarian response affect embryo euploidy? Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy. Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue. A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021. A total of 617 women with 867 PGT-M cycles involving 12874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos). Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all P > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (P = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (P = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (P = 0.001, <0.001, and 0.012, respectively). Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy status due to the fact that blastocyst aneuploidy primarily originates from maternal meiosis. However, sperm factors might have an effect on embryo development and the blastulation rate, and therefore also the number of blastocysts analyzed. The exclusion of patients with severe teratozoospermia and the fact that only ICSI was used as the insemination technique for women undergoing PGT-M contributed to minimize the effect of paternal factors. Ovarian stimulation and response to stimulation did not affect blastocyst euploidy rates in women undergoing PGT-M cycles. However, in women aged 31-40 years old, there was a significant decline in blastulation rates as the number of retrieved oocytes increased. This study was supported by the National Natural Science Foundation of China (Grant No. 81701407, 82301826); the National Key Research and Development Program of China (2022YFC2702901, 2022YFC2703004); China Postdoctoral Science Foundation (2022M710261), and China Postdoctoral Innovation Talent Support Program (BX20220020). There is no conflict of interest. N/A.

Single-cell RNA-sequencing analysis of the effects of frozen-thawed embryo transfer on the transcriptome of trophoblasts

Objectives: Frozen-thawed embryo transfer (FET) is widely used in in vitro fertilization (IVF) clinics but is associated with an increased risk of several pregnancy complications, including large-for-gestational age and placenta-related diseases. However, the effects of FET on placentation remain unclear. Therefore, we used single-cell RNA-sequencing (scRNA-seq) technology to investigate the impact of FET on placental gene expression in different subtypes of trophoblasts. Methods: A mouse model of IVF and FET was constructed to collect placenta tissues. scRNA-seq was performed on placentas from two dams undergoing IVF-embryo transfer and two dams undergoing IVF-FET. Differentially expressed gene (DEG) analyses were performed in different subtypes of trophoblasts. Identified DEGs were PCR validated. Results: The fetal weights and placental efficiency were higher in the FET group than those on the IVF group at E18.5, with no significant difference in placental weights. Subsequently, 55,406 placental cells were captured and annotated. Upregulated DEGs in the FET group in syncytiotrophoblasts (SynTs) and sinusoidal trophoblast giant cells (S-TGCs) within the placental labyrinth were enriched in pathways related to vascular development and oxidative stress, respectively. The expression of the imprinted gene Igf2 in SynTs, S-TGCs, and spongiotrophoblasts was significantly increased. In the junctional zone, FET upregulated the expression of prolactin genes such as Prl3b1 in glycogen trophoblasts (GlyTs) while the downregulated expression of GlyT genes following FET was associated with mesenchyme development. Conclusion: This study first identifies DEGs and enriched pathways in different subtypes of trophoblasts following FET. These genes and pathways may contribute to the increased placental efficiency and fetal weights. Future studies are required to confirm these results and further explore the key mechanisms in placental pathologies.

Vaginal and endometrial microbiome dysbiosis associated with adverse embryo transfer outcomes

BackgroundAssisted reproductive technology (ART) is the most effective method to treat infertility and the pathogenesis of implantation failure after in vitro fertilization-embryo transfer (IVF-ET) is a challenging filed in infertility. Microbes in the female reproductive tract are considered to be associated with gynecological and obstetric diseases. However, its effects on embryo implantation failure are unsured.PurposeThis study aimed to investigate reproductive tract dysbiosis, identify different bacteria in reproductive tract as potential biomarkers of embryo implantation failure and demonstrate the pathogenesis through metabolites analysis.MethodsWe compared the data from 16S rRNA gene and metagenome in reproductive tracts through QIIME2 and HUMAnN2 by the times of embryo implantation failure on 239 infertile patients and 17 healthy women.ResultsOur study revealed a strong positive correlation between Lactobacillus abundance and embryo implantation success (IS) after IVF-ET. The microbial community composition and structure in reproductive tract showed substantially difference between the embryo implantation failure (IF) and healthy control. Moreover, we established a diagnostic model through receiver operating characteristic (ROC) with 0.913 area under curve (AUC) in IS and multiple implantation failures (MIF), verified its effectiveness with an AUC = 0.784 demonstrating microbial community alterations could efficiently discriminate MIF patients. Metagenome functional analyses of vaginal samples from another independent infertile patients after IVF-ET revealed the L-lysine synthesis pathway enriched in IF patients, along with ascended vaginal pH and decreased Lactobacillus abundance.ConclusionsThis study clarifies several independent relationships of bacteria in vagina and endometrial fluid on embryo implantation failure and undoubtedly broadens the understanding about female reproductive health.

Association between Exposure of Rare Earth Elements and Outcomes of In Vitro Fertilization-Embryo Transfer in Beijing

Objective The study aimed to investigate the impact of rare earth elements (REEs) exposure on pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) by analyzing samples from spouses.Methods A total of 141 couples were included. Blood and follicular fluid from the wives and semen plasma from the husbands, were analyzed for REEs using inductively coupled plasma mass spectrometry (ICP-MS). Spearman's correlation coefficients and the Mann–Whitney U test were used to assess correlations and compare REE concentrations among three types of samples, respectively. Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes, while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes.Results Higher La concentration in semen (median 0.089 ng/mL, P = 0.03) was associated with a lower fertilization rate. However, this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection (ICSI) (P = 0.27). In semen, the REEs mixture did not exhibit any significant association with clinical pregnancy.Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate, but not clinical pregnancy rate. This is the first to report REEs concentrations in follicular fluid with La, Ce, Pr, and Nd found at significantly lower concentrations than in serum, suggesting that these four REEs may not accumulate in the female reproductive system. However, at the current exposure levels, mixed REEs exposure did not exhibit reproductive toxicity.

Measuring The Level of The Hormone Progesterone on The Day of Transfer of Fresh and Frozen Embryos and Its Impact on Pregnancy Outcomes

Objective: Prediction of the effect of the hormone progesterone on pregnancy results that measured on the day of transfer of fresh and frozen embryos. Method: This research at reproductive centres in Baghdad from May 2022 to April 2023 examined how serum progesterone levels affect embryo transfers in ICSI procedures in 100 fresh or frozen cycle women. The study examined clinical data and endometrial preparation techniques to determine if progesterone levels affect pregnancy rates. Data were analysed using SPSS to determine how pre-transfer hormonal levels affected implantation and pregnancy outcomes. Participants were selected according on inclusion and exclusion criteria. The study shows that progesterone is essential for IVF embryo transfers. Results: Compared to frozen cycles in females, fresh cycles had greater mean age and progesterone levels but lower COC number and 2PN levels, with no changes in BMI, MII, or injectable MII. Frozen cycles produced more good-grade embryos, whereas fresh cycles produced more fair-grade embryos. There were no differences in the number of "C" embryos. Fresh cycle groups had greater pregnancy rates (59.1%) than frozen cycle groups (38.9%), but progesterone levels did not change between cycle types. Conclusion: The study found that fresh cycles include older participants, greater progesterone but lower COC and 2PN levels, and higher pregnancy rates than frozen cycles. BMI, MII levels, embryo count, poor grade "C" embryos, and progesterone levels associated to pregnancy outcomes did not differ across groups.

Knowledge, attitude, and practice of embryo transfer among women who underwent in vitro fertilization-embryo transfer.

The infertile patient's knowledge, attitude, and practice (KAP) toward embryo transfer may affect treatment outcomes and the mental health of women who underwent in vitro fertilization-embryo transfer (IVF-ET). This study aimed to investigate the KAP of embryo transfer among women who underwent IVF-ET. This cross-sectional study was conducted on women who underwent IVF-ET at our Hospital between May 2023 and November 2023, using a self-designed questionnaire. A total of 614 valid questionnaires were finally included. The mean KAP scores were 19.46 ± 5.06 (possible range: 0 28), 39.41 ± 5.20 (possible range: 12-60), and 48.02 ± 6.75 (possible range: 0-60), respectively. The structural equation model demonstrated that knowledge has a direct effect on attitude (β = 0.27, p < 0.001) and attitude has a direct effect on practice (β = 0.55, p < 0.001) and anxiety (β = 0.59, p < 0.001). Moreover, multivariable linear regression analysis showed that anxiety score [coefficient = 0.09, 95% confidence interval (CI): 0.03-0.16, p = 0.003], BMI (coefficient = 0.09, 95%CI: 0.03-0.16, p = 0.003), education (coefficient = 5.65-6.17, 95%CI: 1.09-10.7, p < 0.05), monthly per capita income (coefficient = 1.20-1.96, 95% CI: 0.21-3.07, p = 0.05), reasons for IVF (coefficient = -1.33-1.19, 95% CI: -2.49-0.09, p < 0.05), and more than 5years of infertility (coefficient = -1.12, 95% CI: -2.11-0.13, p = 0.026) were independently associated with sufficient knowledge. Knowledge (coefficient = 0.19, 95% CI: 0.12-0.26, p < 0.001), anxiety (coefficient = 0.39, 95% CI: 0.34-0.45, p < 0.001), monthly per capita household income >10,000 (coefficient = 1.52, 95% CI: 0.61-2.43, p < 0.001), and three or more cycles of embryo transfer (coefficient = -2.69, 95% CI: -3.94-1.43, p < 0.001) were independently associated with active attitude. Furthermore, attitude (coefficient = 0.21, 95% CI: 0.11-0.30, p < 0.001) and anxiety (coefficient = 0.57, 95% CI: 0.49-0.65, p < 0.001) were independently associated with proactive practice. Women who underwent IVF-ET had inadequate knowledge and negative attitudes but proactive practice toward embryo transfer, which were affected by anxiety, income, and reasons for IVF. It is necessary to strengthen the continuous improvement of patient education to improve the management of embryo transfer.

Acupuncture combined with gonadotropin-releasing hormone agonists improves endometrial receptivity and pregnancy outcome in patients with recurrent implantation failure of in vitro fertilization-embryo transfer.

Gonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET. A total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups. EMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group. Acupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.

Exploring the efficacy and safety of acupuncture versus sham acupuncture for diminished ovarian reserve: study protocol for a multicentre randomised controlled trial

IntroductionThe therapeutic needs of women with diminished ovarian reserve (DOR), coupled with the increasing application of acupuncture in improving ovarian function, have highlighted the need to verify the efficacy and...

Relationship between marital satisfaction and defeat in IVF-ET: based on actor-partner interdependence model approach

Objective A person’s marital satisfaction is a strong predictor of their own mental health outcomes. However, marital satisfaction results from both spouses’ experiences, so a partner’s marital satisfaction also affects his or her mental health outcomes. This study adopted the actor-partner interdependence model approach (APIM) to evaluate the relationship between marital satisfaction and sense of defeat in vitro fertilization-embryo transfer (IVF-ET) couples. Methods and measures In this cross-sectional study, 181 infertile couples undergoing IVF-ET treatment were recruited using the Marital Satisfaction Scale of the ENRICH Marital Quality Questionnaire and Defeat Scale. Through APIM and Pearson analysis, the path relationship between marital satisfaction and defeat was analyzed. Results The varying degrees of defeat in IVF-ET couples, are closely related to actors’ and partners’ marital satisfaction. In terms of actor effects, the Marital Satisfaction of both husbands (β = −0.71, p < 0.001) and wives (β = −0.46, p = 0.001) have a significant effect on individual Defeat. With regard to partner effects, husbands’ Marital Satisfaction (β = −0.23, p = 0.038) has a significant impact on wives’ Defeat and the wives’ Marital Satisfaction (β = −0.45, p = −0.005) has a significant impact on husbands’ Defeat. Conclusion IVF-ET couples must be looked at as a whole, and it is critical to include couples and not just men or women when studying infertility. The importance of their interaction is essential to improve the psychosocial adaptation of infertile couples in IVF-ET treatment.

O-123 Trends and challenges in the practice of ART in China

Abstract China is a large country with a population of over 1.4 billion. In 1988, the first in-vitro fertilization-embryo transfer (IVF-ET) baby was born in Peking University Third Hospital. In the following 3 decades, assisted reproductive technology (ART) has developed rapidly in China, and the availability and accessibility of the ART service have improved markedly. In 2004 totally, only 37 institutions had passed the administrative licensing procedure to carry out ART. While in 2020, 536 institutions obtained the ART license. Since 2016, the total number of ART service cycles(Artificial insemination included)has exceeded 1 million, and the number of babies born has exceeded 300,000, accounting for about 2% of the total live births in China in 2016. At present, assisted reproductive technology has become one of the important medical interventions for the treatment of infertility in China, which has brought good news to infertile couples and their families, and has made great contributions to social harmony and family happiness. Cycles per million population (C/M) in 2009 was 120. In 2020, it has increased to 668, with more and more infertile couples having access to this technique in China. The success rate of assisted reproductive technology remained stable. In 2020, the clinical pregnancy rates (CPR)of conventional IVF and ICSI fresh embryo transfer cycles reached 52.4% and 49.4%, respectively, and the live birth rates were 43.0% and 40.6%, respectively. The clinical pregnancy rate and live birth rate of frozen-thawed embryo cycle were 51.3% and 40.5% per transfer. With the widespread application of embryo freezing technology, the cumulative live birth rate was estimated to reach 49.5% (CLBR estimate) in 2020. The safety monitoring indicators of assisted reproductive technology showed that since 2015, the multiple pregnancy rates of conventional IVF, ICSI and FET have decreased year by year, and have dropped to 22.4%, 21.4% and 17.6% in 2020, respectively. The incidence of moderate-severe ovarian hyper-stimulation syndrome (OHSS) and severe bleeding were also under control, within a reasonable range. Assisted reproductive technology, which involves many medical, social, ethical and legal issues, is a special clinical technology with limit application for medical indication. The Chinese government attaches great importance to the quality and safety management of assisted reproductive technology. A series of management documents such as the Administrative Measures for Human Assisted Reproductive Technology, the Regulations for Human Assisted Reproductive Technology and so forth, have been issued since 2001. Further improvement of key performance indicators (KPIs) correlated with ART quality and safety control is of the top priority and also challenging. In addition, the ART surveillance data in China is still aggregated data, which does not include important indicators such as age stratification, infertile factors or indications and delivery gestational age, maternal and infant outcomes, with some limitations for surveillance. Continuous improvement of data quality, and initiation of cycle-based data collection and security measures of case information are also challenging for the next step.

O-093 Infant mortality after assisted reproductive technology – a Nordic collaborative study on 7,947,575 liveborn children

Abstract Study question Is infant mortality, i.e., mortality up to one year of age, higher after assisted reproductive technology (ART) than after natural conception (NC)? Summary answer Infant mortality was increased in ART-singletons vs NC-singletons, with similar increased mortality across ART fertilization methods. Infant mortality was not increased in ART-twins vs NC-twins. What is known already Children born after ART have an increased risk of poor perinatal outcomes such as preterm birth and low birth weight, mainly due to the higher twin birth rates in the ART population. ART singletons also carry an increased risk of poor perinatal outcomes as compared to their NC counterparts. Studies on consequences of being born after ART are mostly sparse and inconclusive which also applies to studies on infant mortality. Study design, size, duration A Nordic registry-based study including all children born alive in Denmark (1994–2014), Finland (1990–2014), Norway (1984–2015) and Sweden (1985–2015) resulting in a cohort of 171,836 ART-children and 7,775,739 NC-children. Among ART-children 127,248 (74%) were singletons and 42,569 (25%) twins, and among NC-children 7,576,396 (97%) were singletons and 194,775 (3%) twins. Multiples with &amp;gt;2 children were excluded (&amp;lt;0.1%). All singletons and twins were followed until death, emigration or one year of age. Participants/materials, setting, methods Data originated from national ART-, birth-, and causes of death registers. Infant mortality was compared for ART vs NC singletons and ART vs NC twins in separate analyses using Cox proportional hazards model yielding hazard ratios (HRs) with 95% confidence intervals (95% CIs). Infant mortality in singletons and twins was compared for IVF, ICSI, fresh and frozen embryo transfer vs NC counterparts. Cause-specific death analysis accounted for other causes of death as a competing risk. Main results and the role of chance Overall, 515 (4‰) ART- and 26,076 (3‰) NC-singletons and 615 (14‰) ART- and 3317 (17‰) NC-twins died during infancy. Median age at death was 3 (IQR 0–195) and 10 days (IQR 0–245) for ART- and NC-singletons, respectively, and 1 (IQR 0–151) and 2 days (IQR 0–161) for ART- and NC-twins, respectively. After adjusting for country, parity, maternal age, and birth year, the adjusted HR (aHR) for infant mortality was 1.75 (95% CI 1.60–1.91) for ART-singletons vs NC-singletons, and 0.94 (95% CI 0.86–1.03) for ART-twins vs NC-twins. A higher mortality was found consistently among ART-singletons born after IVF, ICSI, fresh embryo transfer and frozen embryo transfer vs NC-singletons. Infant mortality was consistently similar between ART-twins and NC-twins across treatment methods. Leading causes of death were conditions originating in the perinatal period (23% and 47% of deaths among singletons and twins) with aHR 1.87 (95% CI 1.65–2.12) for ART-singletons vs NC-singletons, and aHR 0.97 (95% CI 0.86–1.10) for ART-twins vs NC-twins, and congenital malformations (19% and 11% of deaths among singletons and twins) with aHR 1.31 (95% CI 1.09–1.58) for singletons and aHR 1.37 (95% CI 1.08–1.74) for ART-twins vs NC-twins. Limitations, reasons for caution Observational studies are prone to confounding. Despite adjustment for some major confounders, residual confounding from underlying parental conditions cannot be excluded. Causes of death may be more complex than the causes registered. Further, 44% of deaths among NC and 12% of deaths in ART were without an assigned cause. Wider implications of the findings Findings that infant mortality is increased among ART- vs NC-singletons corresponds with previous findings of poorer perinatal outcomes in this group. Risks were similar across ART fertilization methods and cryopreservation status. Trial registration number Not applicable

O-203 Comparing viable and non-viable IVF early pregnancy measurements: does knowledge of gestational age using date of ET potentially change miscarriage diagnosis guidelines in IVF patients

Abstract Study question In IVF pregnancies with known embryo transfer (ET) dates, can gestational age as well as ultrasound measurements be used to diagnose miscarriage? Summary answer Early pregnancy measurements vary at fixed gestational ages based on ET. However, there is a specific time cut-off where an empty gestational sac indicates miscarriage. What is known already Current guidelines state that when ultrasound findings show a pregnancy of unknown viability, a repeat scan must be performed either 7 or 14 days later (depending on the presence of an embryo or gestation sac size) to confirm viability, irrespective of the LMP based gestational age. This definition only considers ultrasound measurements, and even when the pregnancy dates thought to be certain and based on day of ET date, there are no exceptions to this guidance. Study design, size, duration This was a retrospective cohort study within a London tertiary unit, Wolfson Clinic, Hammersmith Hospital, Imperial College Healthcare NHS Trust over a 36-month time period. We collated data from both fresh and frozen cycle IVF pregnancies over four years: Jan 1st 2019 to December 31st 2021. Participants/materials, setting, methods In this unit, patients undergoing fresh or frozen IVF cycles, have an embryo transfer at Day3-6 of development. We included any patient with a confirmed intrauterine pregnancy at first scan (5-8 weeks gestation) for analysis of pregnancy outcomes. The data collected included date of embryo transfer (ET), embryo age at transfer, and early pregnancy measurements using ultrasound. The endpoint was viability at the 11-14 week dating scan. Main results and the role of chance 1161 IVF embryo transfers were included in the study, 677 (58.3%) frozen and 484 (41.7%) fresh cycles. 892 (76.8%) remained viable at 11-14 weeks and 269 (23.2%) were non-viable. Pregnancies resulting in viable pregnancies had a range of CRL (≤16mm) and empty mean gestation sac diameter (MSD) (≤11mm) measurements at each expected age by ET date (≤8 weeks gestation). At 49 days CRL varied from 1mm to 17mm, and at 42 days empty MSD measurements varied from 7 to 18mm. This shows that a range in embryo and gestation sac sizes will be seen in subsequently shown to be viable pregnancies despite the apparent exact gestation being known based on ET. This may relate to both differing embryo growth rates and timing of implantation. A Kolmogorov-Smirnov test was applied to compare the viable and miscarriage cohort CRL measurements in relation to expected age by ET. The result: 0.610, p-value=1.33 x10-15, demonstrated a significant difference in embryo size between viable and non-viable pregnancies with known ET dates. All pregnancies where the scan showed an empty gestational sac (n = 157) at 47 days gestation by ET date, had a 100% positive predictive value with a 100% specificity (CI:90.1-100.0) for miscarriage. Limitations, reasons for caution The sample was powered to 0.9, significance level 0.05. Analysis demonstrated 100% positive predictive value with 100% specificity (CI:90.1-100.0), to confirm miscarriage with an empty gestation sac ≥47days age by ET date. A larger cohort size from different centres is needed to reduce the confidence interval and confirm the findings. Wider implications of the findings There is significant variation in CRL and MSD size between viable pregnancies of the same gestational age by ET. However, we found &amp;gt;47 days gestation an empty gestation sac resulted in miscarriage. If confirmed in larger studies this may permit women to be given an earlier definitive diagnosis of miscarriage. Trial registration number Audit registration GRM_104 Imperial Healthcare NHS Trust

Prestimulation parameters predicting the pregnancy outcomes after IVF-ET in patients with unexplained infertility.

Assisted Reproductive Technologies (ART) are considered to be the most effective treatment option for unexplained infertility. This study aims to investigate the pregnancy outcomes of women who received in-vitro fertilization-embryo transfer (IVF-ET) treatment for unexplained infertility and the contributing factors affecting these outcomes. The present study included 789 consecutive women with unexplained infertility who were treated with IVF-ET at the ART Clinic of the Health Sciences University, Ankara Etlik Zübeyde Hanım Gynecology Training and Research Hospital between January 2007 and December 2019. The contributing factors affecting these outcomes, such as body mass index (BMI), basal follicle-stimulating hormone (FSH), and antimullerian hormone (AMH), were evaluated retrospectively. Clinical pregnancy per cycle was 19.8% among patients recruited. No statistically significant difference was detected in terms of age, infertility duration, and BMI of the patients who achieved pregnancy and who failed to get pregnant after IVF-ET treatment. The basal FSH level was found to be significantly lower (p=0.001), and the AMH level was significantly higher in patients who had clinical pregnancy (p=0.001). The basal AMH cut-off value was calculated to be 3.34 ng/mL, and the basal FSH cut-off value was calculated as 7.26 IU/L for the prediction of clinical pregnancy. IVF-ET treatment can be applied as a successful treatment option in unexplained infertility cases. Although the basal FSH and AMH values ​are not the cut-off values that have high sensitivity and specificity, they are considered to be associated with pregnancy rates.

First-trimester ultrasound diagnosis and risk factor analysis of cesarean scar pregnancy after in vitro fertilization-embryo transfer.

Cesarean scar pregnancy (CSP) is one of the rarest ectopic pregnancies which may be associated with life-threatening complications. Owing to the rarity of CSP, little is known about it. This study aimed to evaluate the value of the first-trimester transvaginal sonography (TVS) diagnosis and the risk factors of CSP after in vitro fertilization-embryo transfer (IVF-ET). This was a retrospective study of women undergoing IVF-ET between January 2013 and December 2018. Women who were diagnosed with a CSP using TVS and confirmed by surgery and histological examination were included. The clinical data and ultrasound findings were collected and analyzed. Univariate and multivariate logistic regression analyses were performed for evaluation of possible influence factors. Diagnostic parameters including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TVS were calculated for the diagnosis of CSP. Overall, 75,438 consecutive women who underwent IVF-ET had received TVS during this period. Of these, 4,817 women (6.4%) had a history of cesarean section and 83 cases were found to have a CSP. Due to the absence of histological data, 19 cases treated conservatively were excluded. Finally, 64 cases were included, among whom 63 cases were correctly diagnosed [including 17 cases of heterotopic CSP (HCSP)] and 1 case was missed using TVS. Another 1 case of inevitable miscarriage was misdiagnosed as a CSP. The maternal age at the initial scan [34.0 (range, 26.0-44.0) years], the infertility duration [4.0 (range, 1-12) years], and the initial diagnostic time after ET [27 (range, 20-50) days] were recorded. A gestational sac (GS) was observed in all 63 cases during ultrasound examinations, including 28 with fetal pole, 25 with a yolk sac only, and 10 with an empty sac. The sensitivity and specificity of first-trimester TVS in diagnosing CSP were 98.44% and 99.98%, respectively; the PPV and NPV were 98.44% and 99.98%, respectively. Multivariate logistic regression analysis showed thinner endometrial thickness (ET) on transfer day [adjusted odds ratio (aOR): 0.83; 95% confidence interval (CI): 0.76-0.93, P<0.001] and multiple ET (aOR 53.60, 95% CI: 5.31-1,736.00, P=0.008) were independent risk factors for CSP and HCSP, respectively. First-trimester TVS performed by an experienced sonographer has a high sensitivity for making the correct diagnosis of CSP after IVF-ET, which is helpful for clinical intervention and avoiding severe complications. For patients with a history of cesarean section, thinner ET on the transfer day and bigger body mass index (BMI) seem to be risk factors for CSP; single blastocyst transfer should be recommended to decrease the possibility of HCSP. The clinical significance of this study still needs to be considered.

Clinical outcomes of fresh and frozen embryos transfer after in vitro fertilization in spouses of patients with severely low sperm concentration and motility.

To compare the pregnancy and neonatal outcomes of in vitro fertilization-embryo transfer (IVF-ET) with fresh or frozen embryos in spouses of patients with severely low sperm concentration and motility. A total of 2300 patients whose spouses have severely low sperm concentration and motility underwent IVT-ET in the Reproduction Medicine Center, Sir Run Run Shaw Hospital from April 2018 to April 2022. After applying the propensity score matching (PSM), 473 fresh embryo transferred cycles and 473 frozen embryo transferred cycles were selected for the study, and the pregnancy and neonatal outcomes were compared between the two groups. There were no significant differences in pregnancy outcomes and neonatal outcomes between fresh and frozen embryo groups (all P>0.05). In the stratification analysis, the number of retrieved oocytes in the fresh good-quality embryo transfer group was significantly increased compared with the fresh poor-quality embryo group (P<0.05), but the very early pregnancy loss rates were similar between the two groups (P>0.05), while the rate in fresh good-quality embryo transfer group was significantly higher than that in the frozen good-quality embryo transfer group (P<0.05). Among different age groups of women, the number of retrieved oocytes and the level of estrogen in the fresh embryo transfer group was significantly higher in the 20 to <30 years old group than that in the 30 to <35 years old group (both P<0.05), but the clinical pregnancy rate was lower in the 20 to <30 years old group than that in the 30 to <35 years old group (P>0.05). Additionally, the very early pregnancy loss was significantly increased in the fresh embryo group compared with the frozen embryo group in the 20 to <30 years age group (P<0.05). There were no significant differences in pregnancy and neonatal outcomes between fresh and frozen embryo transfer in spouses of patients with severely low sperm concentration and motility undergoing IVF-ET. Due to the shorter transfer times, less embryo freezing damage and reduced costs, fresh embryo transfer can be considered as the first choice. However, it is not necessary to pursue fresh embryo transfer if maternal oestrogen levels are too high and there is a tendency of overstimulation.

Effect of Tiaojing Cuyun acupuncture therapy on pregnancy outcomes in women with diminished ovarian reserve undergoing IVF-ET: a cohort study

To assess the effect of Tiaojing Cuyun acupuncture therapy (acupuncture for regulating menstruation and promoting pregnancy) on pregnancy outcomes in patients with diminished ovarian reserve (DOR) undergoing in vitro fertilization-embryo transfer (IVF-ET). Eighty women with DOR were divided into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 1 case dropped out) according to whether Tiaojing Cuyun acupuncture therapy was given or not. In the control group, IVF-ET was delivered. In the observation group, before IVF-ET, Tiaojing Cuyun acupuncture therapy was given. Two groups of acupoints were used alternatively, including Baihui (GV 20), Shenting (GV 24), Benshen (GB 13), Zhongwan (CV 12), Guanyuan (CV 4), and bilateral Tianshu (ST 25), Shenshu (BL 23), Ciliao (BL 32), etc. Acupuncture was operated once every other day, three interventions a week, for 12 weeks. The primary outcome was clinical pregnancy rate (CPR). Secondary outcomes included the total days and amount of gonadotropin (Gn) used, the number of oocytes retrieved, the number of oocytes in metaphase of second meiosis (MⅡ), the number of transferable embryos, the number of high-quality embryos, the cycle cancellation rate, the positive rate of human choriogonadotropin (HCG), the embryo implantation rate, live birth rate (LBR), the basal serum levels of sex hormones (follicular stimulating hormone [FSH], estradiol (E2), FSH/luteinizing hormone [LH]) and antral follicle count (AFC). CPR in the observation group was higher than that in the control group (53.8% [21/39] vs. 17.9% [7/39], P<0.05). The results of the number of oocytes retrieved, the number of oocytes in MⅡ, the number of transferable embryos, the number of high-quality embryos, the positive rate of HCG, the embryo implantation rate, and LBR in the observation group were higher than those in the control group (P<0.05). The serum level of FSH and FSH/LH in the observation group were lower thau those in the control group (P<0.05). The differences were not significant statistically in the total days and amount of Gn used, the cycle cancellation rate, serum level of E2 and AFC between the two groups (P>0.05). Logic regression analysis showed that CPR increased in the observation group when compared with that of the control group (OR = 5.33, 95%CI: 1.90-14.97, P = 0.001). Acupuncture can improve the pregnancy outcomes of DOR women undergoing IVF-ET.

Value of estrogen pretreatment in patients with diminished ovarian reserve and elevated FSH on a line antagonist regimen: a retrospective controlled study.

The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ovarian reserve (DOR). During in vitro fertilization-embryo transfer (IVF-ET) treatment, luteal phase estrogen pretreatment may enhance follicular development synchronization and yield of mature oocytes. However, the effect of estrogen pretreatment in DOR patients with elevated basal follicle-stimulating hormone (FSH) levels has not been well studied. We retrospectively analyzed the clinical data of patients with elevated basal FSH levels and DOR (401 cycles) who underwent IVF/intracytoplasmic monosperm injection (ICSI)-assisted conception. Both groups were treated with a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen and were further divided into two groups according to whether they received luteal estrogen pretreatment. There were 79 patients in the estrogen pretreatment group and 322 patients in the control group. On the second day of the menstrual cycle, gonadotropin (Gn) stimulation of the ovaries was initiated. The general characteristics, clinical, biological parameters and outcomes of the two groups were compared. The basic profiles of the two groups were similar (P > 0.05). More patients in the pretreatment group showed FSH rebound after gonadotropin (Gn) initiation, resulting in a significantly higher number of Gn days and total Gn than those in the control group (P < 0.05). There was no statistically significant difference in the number of days of antagonist use, follicle output rate (FORT), number of metaphase II(MII)eggs obtained, number of Two pronuclei (2PN) fertilized, number of D3 quality embryos, blastocyst formation rate, fresh embryo clinical pregnancy rate, cumulative pregnancy rate, and non-transferable embryo rate between the two groups (P > 0.05). The use of luteal phase estrogen pretreatment in patients with elevated basal FSH combined with DOR resulted in high FSH levels after the release of negative feedback, which was detrimental to early follicular growth, did not increase the follicular output rate, may have increased the use and duration of controlled ovarian stimulation drugs, and did not increase the number of eggs gained or improve clinical outcomes.