Background: Obesity is a worldwide problem affecting the health of millions of people throughout the life course. Studies reveal that obesity impairs sperm parameters and epigenetics, potentially influencing embryonic development.Objective: To investigate the association between preconceptional paternal body mass index (BMI) and embryo morphokinetics using a time-lapse incubator and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. Materials and methods:Participants were recruited from a tertiary hospital in this prospective periconceptional cohort study. A total of 211 men were included: 86 with normal weight (BMI < 25.0), 94 overweight (BMI 25-29.9), and 41 obese (BMI ≥ 30).These men were part of a couple that underwent IVF/ICSI treatment with ejaculated sperm after which 757 embryos were cultured in a time-lapse incubator. The main outcome parameters consisted of fertilization rate, embryo developmental morphokinetics, embryo quality assessed by a time-lapse prediction algorithm (KIDScore), and live birth rate.Results: A higher paternal BMI was associated with faster development of the preimplantation embryo, especially during the first cleavage divisions (t2: −0.11 h (p = 0.05) and t3: −0.19 h (p = 0.01)). Embryo quality using the KIDScore was not altered. The linear regression analysis, after adjustment for confounders (paternal age, ethnicity, smoking, alcohol use, education, total motile sperm count, and maternal age and BMI), showed an inverse association between paternal BMI and fertilization rate (effect estimate: −0.01 (p = 0.002)), but not with the live birth rate.Discussion and conclusion: Our data demonstrate that a higher preconceptional paternal BMI is associated with a reduced fertilization rate in IVF/ICSI treatment. Our findings underline the importance of a healthy paternal weight during the preconception period.
Background Overweight 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. Methods From 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. Results After 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). Conclusions Higher 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.
STUDY QUESTION Does frozen-thawed or fresh embryo transfer (ET) influence utero-placental (vascular) development, when studied using three-dimensional (3D) ultrasound and virtual reality imaging techniques? SUMMARY ANSWER In the first trimester, placental developmental parameters, that is, placental volume (PV) and utero-placental vascular volume (uPVV), were comparable between pregnancies resulting from frozen-thawed ET, fresh ET and natural conception; and in the second and the third trimester, uterine artery Doppler indices were lower in pregnancies after frozen-thawed ET compared to pregnancies after fresh ET and natural conception. WHAT IS KNOWN ALREADY Pregnancies after frozen-thawed ET are at risk of developing placenta-related pregnancy complications. There is strong evidence that impaired first-trimester spiral artery remodelling is involved in the pathophysiology of these complications. Studies on longitudinal placental development in pregnancies with different modes of conception, that is, after frozen-thawed ET, fresh ET or natural conception, are lacking. STUDY, DESIGN, SIZE, DURATION Women with singleton pregnancies were included before 10 weeks of gestation, between January 2017 and July 2018, as a subcohort of the ongoing Rotterdam Periconception cohort. Results were partially validated in 722 women from the total cohort, which was conducted from November 2010 onwards. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 214 women, of whom 32 conceived after frozen-thawed ET, 56 conceived after fresh ET and 126 conceived naturally, were selected. PV and uPVV measurements were obtained at 7, 9 and 11 weeks of gestation by transvaginal 3D (power Doppler) ultrasound. The uterine artery pulsatility index (UtA-PI) and resistance index (UtA-RI) were measured transvaginally at 7, 9, 11 and 13 weeks and abdominally at 22 and 32 weeks of gestation by pulsed wave Doppler ultrasound. In the validation cohort, the PV was measured in 722 women. Associations between mode of conception and placental development were studied using linear mixed models. MAIN RESULTS AND THE ROLE OF CHANCE First-trimester parameters of placental development, that is, PV, uPVV, UtA-PI and UtA-RI, were comparable between pregnancies after frozen-thawed and fresh ET and naturally conceived pregnancies. In our validation cohort, comparable results were found for PV. However, the second- and third-trimester UtA-PI and UtA-RI in pregnancies after frozen-thawed ET were significantly lower than in pregnancies after fresh ET (βUtA-PI −0.158 (95% CI: −0.268, −0.048), P = 0.005; βUtA-RI −0.052 (95% CI: −0.089, −0.015), P = 0.006). The second- and third-trimester uterine artery indices in pregnancies after fresh ET were comparable to those in pregnancies after natural conception. LIMITATIONS, REASONS FOR CAUTION The main limitation of this study is the lack of power to optimally detect differences in placental development and placenta-related pregnancy outcomes between pregnancies after different modes of conception. Moreover, our population was selected from a tertiary hospital and included a relatively limited number of pregnancies. Therefore, external validity of the results should be confirmed in a larger sample size. WIDER IMPLICATIONS OF THE FINDINGS These findings indicate no significant impact of conception mode on early placental development and a beneficial impact for frozen-thawed ET on the second- and third-trimester Doppler indices. This suggests that frozen-thawed ET may not be as detrimental for placental perfusion as previous research has demonstrated. As the number of clinics applying the ‘freeze-all strategy’ increases, future research should focus on establishing the optimal uterine environment, with regards to hormonal preparation, prior to ET to reduce placental-related pregnancy complications after frozen-thawed ET. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Erasmus MC Medical Research Advisor Committee’s ‘Health Care Efficiency Research’ program and the department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Center, Rotterdam, The Netherlands. JSEL reports grants and personal fees from Ferring, personal fees from Titus Healthcare, grants and personal fees from Ansh Labs, grants from NIH, grants from Dutch Heart Association and grants from ZonMW outside the submitted work. None of the other authors have a conflict of interest. TRIAL REGISTRATION NUMBER Registered at the Dutch Trial Register (NTR6684).
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