Living in a low socioeconomic status neighbourhood is associated with lower cumulative ongoing pregnancy rate after IVF treatment.

RESEARCH QUESTION: Does an association exist between neighbourhood socioeconomic status (SES) and the cumulative rate of ongoing pregnancies after 2.5 years of IVF treatment? DESIGN: A retrospective observational study involving 2669 couples who underwent IVF or IVF and intracytoplasmic sperm injection treatment between 2006 and 2020. Neighbourhood SES for each couple was determined based on their residential postal code. Subsequently, SES was categorized into low (p80). Multivariable binary logistic regression analyses were conducted, with the cumulative ongoing pregnancy within 2.5 years as the outcome variable. The SES category (reference category: high), female age (reference category: 32-36 years), body mass index (reference category: 23-25 kg/m2), smoking status (yes/no), number of oocytes after the first ovarian stimulation, embryos usable for transfer or cryopreservation after the first cycle, duration of subfertility before treatment and insemination type were used as covariates. RESULTS: A variation in ongoing pregnancy rates was observed among SES groups after the first fresh embryo transfer. No difference was found in the median number of IVF treatment cycles carried out. The cumulative ongoing pregnancy rates differed significantly between SES groups (low: 44%; medium: 51%; high: 56%; P < 0.001). Low neighbourhood SES was associated with significantly lower odds for achieving an ongoing pregnancy within 2.5 years (OR 0.66, 95% CI 0.52 to 0.84, P < 0.001). CONCLUSION: Low neighbourhood SES compared with high neighbourhood SES is associated with reducing odds of achieving an ongoing pregnancy within 2.5 years of IVF treatment.

A higher preconceptional paternal body mass index influences fertilization rate and preimplantation embryo development.

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.

Preconceptional Maternal Vegetable Intake and Paternal Smoking Are Associated with Pre-implantation Embryo Quality.

Inadequate nutrition and lifestyle behaviors, particularly during the periconception period, are associated with a negative impact on embryonic and subsequent fetal development. We investigated the associations between parental nutritional and lifestyle factors and pre-implantation embryo development. A total of 113 women and 41 partners, with a corresponding 490 embryos, who underwent intracytoplasmic sperm injection (ICSI) treatment subscribed to the mHealth coaching platform "Smarter Pregnancy." At baseline, nutrition and lifestyle behaviors (intake of fruits, vegetables, folic acid, and smoking and alcohol use) were identified and risk scores were calculated. A lower risk score represents healthier behavior. As outcome measure, a time-lapse morphokinetic selection algorithm (KIDScore) was used to rank pre-implantation embryo quality on a scale from 1 (poor) to 5 (good) after being cultured in the Embryoscope™ time-lapse incubator until embryonic day 3. To study the association between the nutritional and lifestyle risk scores and the KIDScore in men and women, we used a proportional odds model. In women, the dietary risk score (DRS), a combination of the risk score of fruits, vegetables, and folic acid, was negatively associated with the KIDScore (OR 0.86 (95% CI 0.76 to 0.98), p = 0.02). This could mainly be attributed to an inadequate vegetable intake (OR 0.76 (95% CI 0.59 to 0.96), p = 0.02). In men, smoking was negatively associated with the KIDscore (OR 0.53 (95% CI 0.33 to 0.85), p < 0.01). We conclude that inadequate periconceptional maternal vegetable intake and paternal smoking significantly reduce the implantation potential of embryos after ICSI treatment. Identifying modifiable lifestyle risk factors can contribute to directed, personalized, and individual recommendations that can potentially increase the chance of a healthy pregnancy.

The fate of the mosaic embryo: chromosomal constitution and development of Day 4, 5 and 8 human embryos.

BACKGROUND: Post-zygotic chromosome segregation errors are very common in human embryos after in vitro fertilization, resulting in mosaic embryos. However, the significance of mosaicism for the developmental potential of early embryos is unknown. We assessed chromosomal constitution and development of embryos from compaction to the peri-implantation stage. METHODS: From 112 cryopreserved Day 4 human embryos donated for research, 21 were immediately fixed and all cells were analysed by fluorescent in situ hybridization (FISH) for chromosomes 1, 7, 13, 15, 16, 18, 21, 22, X and Y. The remaining 91 embryos were thawed, with 54 embryos undergoing biopsy of one or two cells which were fixed and analysed by FISH. Biopsied embryos were kept in standard culture conditions for 24 h. Embryos arrested before cavitation (n = 24) were fixed whereas developing Day 5 blastocysts (n = 24) were co-cultured for a further 72 h on an endometrial monolayer followed by fixation. Cell numbers were counted and all nuclei were analysed by FISH. Data from a previous FISH analysis on cryopreserved good-quality Day 5 blastocysts (n = 36) were also included in the present study. RESULTS: FISH analysis was successful for 18 Day 4 fixed embryos and, according to our definition, 83% were mosaic and 11% showed a chaotic chromosomal constitution. FISH analysis of two blastomeres from Day 4 developing embryos showed that 54% were mosaic, 40% were normal and 6% were abnormal. Analysis of Day 4, 5 and 8 whole embryos showed a decrease in incidence of mosaicism over time, from 83% on Day 4 to 42% on Day 8. A significant positive correlation was observed between the total cell number and the percentage of normal cells in developing Day 5 and Day 8 embryos but not in developing Day 4 or embryos arrested before cavitation. CONCLUSIONS: These data suggest that both the developmental arrest of a significant proportion of mosaic embryos on Day 4, and the cell death or reduced proliferation of aneuploid cells within an embryo may be responsible for the observed decrease of aneuploid blastomeres from compaction to the peri-implantation stage.

Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial.

BACKGROUND: To test whether ovarian stimulation for in-vitro fertilization (IVF) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development, preimplantation genetic screening of embryos was employed in a prospective, randomized controlled trial, comparing two ovarian stimulation regimens. METHODS: Infertile patients under 38 years of age were randomly assigned to undergo a mild stimulation regimen using gonadotrophin-releasing hormone (GnRH) antagonist co-treatment (67 patients), which does not disrupt secondary follicle recruitment, or a conventional high-dose exogenous gonadotrophin regimen and GnRH agonist co-treatment (44 patients). Following IVF, embryos were biopsied at the eight-cell stage and the copy number of 10 chromosomes was analysed in 1 or 2 blastomeres. RESULTS: The study was terminated prematurely, after an unplanned interim analysis (which included 61% of the planned number of patients) found a lower embryo aneuploidy rate following mild stimulation. Compared with conventional stimulation, significantly fewer oocytes and embryos were obtained following mild stimulation (P < 0.01 and < 0.05, respectively). Consequently, both regimens generated on average a similar number (1.8) of chromosomally normal embryos. Differences in rates of mosaic embryos suggest an effect of ovarian stimulation on mitotic segregation errors. CONCLUSIONS: Future ovarian stimulation strategies should avoid maximizing oocyte yield, but aim at generating a sufficient number of chromosomally normal embryos by reduced interference with ovarian physiology.