Dataset Information

Human oocyte area is associated with preimplantation embryo usage and early embryo development: the Rotterdam Periconception Cohort.

ABSTRACT:

Purpose

To investigate the association between oocyte area and fertilization rate, embryo usage, and preimplantation embryo development in order to establish if oocyte area can be a marker for optimal early embryo development.

Methods

From 2017 to 2020, 378 couples with an indication for IVF (n = 124) or ICSI (n = 254) were included preconceptionally in the Rotterdam Periconception Cohort. Resulting oocytes (n = 2810) were fertilized and submitted to time-lapse embryo culture. Oocyte area was measured at the moment of fertilization (t0), pronuclear appearance (tPNa), and fading (tPNf). Fertilization rate, embryo usage and quality, and embryo morphokinetics from 2-cell stage to expanded blastocyst stage (t2-tEB) were used as outcome measures in association with oocyte area. Oocytes were termed "used" if they were fertilized and embryo development resulted in transfer or cryopreservation, and otherwise termed "discarded". Analyses were adjusted for relevant confounders.

Results

Oocyte area decreased from t0 to tPNf after IVF and ICSI, and oocytes with larger area shrank faster (β - 12.6 µm²/h, 95%CI - 14.6; - 10.5, p < 0.001). Oocytes that resulted in a used embryo were larger at all time-points and reached tPNf faster than oocytes that fertilized but were discarded (oocyte area at tPNf in used 9864 ± 595 µm² versus discarded 9679 ± 673 µm², p < 0.001, tPNf in used 23.6 ± 3.2 h versus discarded 25.6 ± 5.9 h, p < 0.001). Larger oocytes had higher odds of being used (oocyte area at tPNf OR_used 1.669, 95%CI 1.336; 2.085, p < 0.001), were associated with faster embryo development up to the morula stage (e.g., t9 β - 0.131 min, 95%CI - 0.237; - 0.025, p = 0.016) and higher ICM quality.

Conclusion

Oocyte area is an informative marker for the preimplantation development of the embryo, as a larger oocyte area is associated with higher quality, faster developing embryos, and higher chance of being used. Identifying determinants associated with oocyte and embryo viability and quality could contribute to improved preconception care and subsequently healthy pregnancies.

SUBMITTER: Wiegel RE

PROVIDER: S-EPMC10310608 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Human oocyte area is associated with preimplantation embryo usage and early embryo development: the Rotterdam Periconception Cohort.

Wiegel Rosalieke E RE Rubini Eleonora E Rousian Melek M Schoenmakers Sam S Laven Joop S E JSE Willemsen Sten P SP Baart Esther B EB Steegers-Theunissen Régine P M RPM

Journal of assisted reproduction and genetics 20230502 6

<h4>Purpose</h4>To investigate the association between oocyte area and fertilization rate, embryo usage, and preimplantation embryo development in order to establish if oocyte area can be a marker for optimal early embryo development.<h4>Methods</h4>From 2017 to 2020, 378 couples with an indication for IVF (n = 124) or ICSI (n = 254) were included preconceptionally in the Rotterdam Periconception Cohort. Resulting oocytes (n = 2810) were fertilized and submitted to time-lapse embryo culture. Ooc ...[more]

PMID: 37129725

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Project description:Study questionCould circulating maternal prorenin serve as a proxy for oocyte and preimplantation embryo development, assessed by time-lapse parameters and clinical treatment outcomes?Summary answerHigh circulating maternal prorenin concentrations after ovarian stimulation associate with a larger oocyte area, faster cleavage divisions from the five-cell stage onwards and increased chance of successful implantation.What is known alreadyAfter ovarian stimulation, circulating prorenin (renin's precursor), is largely ovary-derived. Prorenin may contribute to ovarian angiotensin synthesis, which is relevant in reproduction given its role in follicular development and oocyte maturation.Study design, size, durationProspective observational cohort study including couples requiring fertility treatment from May 2017 as a subcohort of the ongoing Rotterdam Periconception Cohort conducted in a tertiary referral hospital.Participants/materials, setting, methodsBetween May 2017 and July 2020, 309 couples with an indication for IVF treatment or ICSI were included. Resulting embryos (n = 1024) were submitted to time-lapse embryo culture. Time of fertilization (t0), pronuclear appearance (tPNa), and fading (tPNf) as well as the exact timing of reaching the two- to eight-cell stage (t2-t8), the start of blastulation (tSB), reaching the full (tB), and expanded blastocyst (tEB) were retrospectively recorded. Oocyte area was measured at t0, tPNa, and tPNf. Prorenin was determined at the day of embryo transfer.Main results and the role of chanceAfter adjustment for patient- and treatment-related factors, linear mixed modeling showed that higher prorenin concentrations associate with a larger oocyte area at tPNa (β 64.45 µm2, 95% CI 3.26; 125.64, P = 0.04), and faster progression from five-cell stage onwards (e.g. β8-cell -1.37 h, 95% CI -2.48; -0.26, P = 0.02). Prorenin associated positively with pre-transfer outcomes (e.g. βfertilized oocytes 2.09, 95% CI 1.43; 2.75, P < 0.001) and implantation (odds ratio+β-hCG-test: 1.79, 95% CI 1.06; 3.08, P = 0.03), but not with live birth.Limitations, reasons for cautionThis prospective observational study provides associations and therefore residual confounding cannot be excluded and causality has to be shown in intervention studies.Wider implications of the findingsTheca cell-derived factors, such as prorenin, may help to clarify the underlying endocrine mechanism of oocyte maturation and embryo development, with a special focus on the (patho)physiological reproductive role of prorenin and the identification of factors influencing its secretion and activity, which is of great added value for improving embryo selection and predicting implantation and pregnancy outcomes. This will bring us to investigate which determinants of oocyte quality and embryo development should take center stage in developing preconception care strategies.Study funding/competing interest(s)This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, and the Erasmus MC Medical Research Advisor Committee's 'Health Care Efficiency Research' program (OZBS72.16080). The authors have no competing interests to disclose.Trial registration numberN/A.

Project description:BackgroundOverweight and obesity affect millions of people globally, which has also serious implications for reproduction. For example, treatment outcomes after in vitro fertilisation (IVF) are worse in women with a high body mass index (BMI). However, the impact of maternal BMI on embryo quality is inconclusive. Our main aim is to study associations between preconceptional maternal BMI and morphokinetic parameters of preimplantation embryos and predicted implantation potential. In addition, associations with clinical IVF outcomes are investigated.MethodsFrom a tertiary hospital, 268 women undergoing IVF or IVF with intracytoplasmic sperm injection (ICSI) were included; 143 normal weight, 79 overweight and 46 obese women. The embryos of these women were cultured in the EmbryoScope, a time-lapse incubator. The morphokinetic parameters of preimplantation embryos and predicted implantation potential, assessed by the KIDScore algorithm were longitudinally evaluated as primary and secondary outcomes, respectively. The tertiary outcomes included clinical outcomes, i.e., fertilization, implantation and live birth rate.ResultsAfter adjustment for patient- and treatment-related factors, we demonstrated in 938 embryos that maternal BMI is negatively associated with the moment of pronuclear appearance (βtPNa -0.070 h (95%CI -0.139, -0.001), p = 0.048), pronuclear fading (βtPNf -0.091 h (95%CI -0.180, -0.003), p = 0.043 and the first cell cleavage (βt2 -0.111 h (95%CI -0.205, -0.016), p = 0.022). Maternal BMI was not significantly associated with the KIDScore and tertiary clinical treatment outcomes. In embryos from couples with female or combined factor subfertility, the impact of maternal BMI was even larger (βtPNf -0.170 h (95%CI -0.293, -0.047), p = 0.007; βt2 -0.199 h (95%CI -0.330, -0.067), p = 0.003). Additionally, a detrimental impact of BMI per point increase was observed on the KIDScore (β -0.073 (se 0.028), p = 0.010).ConclusionsHigher maternal BMI is associated with faster early preimplantation development. In couples with female or combined factor subfertility, a higher BMI is associated with a lower implantation potential as predicted by the KIDScore. Likely due to power issues, we did not observe an impact on clinical treatment outcomes. However, an effect of faster preimplantation development on post-implantation development is conceivable, especially since the impact of maternal BMI on pregnancy outcomes has been widely demonstrated.

Project description:Study questionIs periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population?Summary answerWomen with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (<p3), compared to women using only FA.What is known alreadyPericonceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA.Study design, size, durationA prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020.Participants/materials, setting, methodsWe included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires.Main results and the role of chanceThis study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA.Limitations, reasons for cautionFollowing the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS.Wider implications of the findingsOur findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended.Study funding/competing interest(s)This research was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and the ZonMw grant Open Competition 2018 (09120011910046). The authors declare that they have no conflict of interest.Trial registration numberNTR4356.

Dataset Information

Human oocyte area is associated with preimplantation embryo usage and early embryo development: the Rotterdam Periconception Cohort.

Purpose

Methods

Results

Conclusion

Publications

Human oocyte area is associated with preimplantation embryo usage and early embryo development: the Rotterdam Periconception Cohort.

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