Summer is not associated with higher live birth rates in fresh IVF/ICSI cycles: a population-based nationwide registry study

Abstract

STUDY QUESTION Is summer associated with higher live birth rate after fresh IVF/ICSI? SUMMARY ANSWER There was no support for a higher live birth rate after fresh IVF/ICSI when treatment was performed during the summer season. WHAT IS KNOWN ALREADY Seasonal variations in human natural conception and birth rates are well described. It has been hypothesized that serum vitamin D, levels of which are associated with sun exposure, may have a role in human natural conception rates. However, the association between seasons and IVF outcomes has not yet been clarified and conflicting reports have been published. Furthermore, it has been suggested that women with normal vitamin D levels have a better pregnancy outcome after ART compared to those with vitamin D insufficiency. STUDY DESIGN, SIZE, DURATION A nationwide, register-based cohort study including all first time fresh IVF/ICSI treatments (n = 52 788) leading to oocyte retrieval in Sweden between 2009 and 2018 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS All first time fresh IVF/ICSI cycles leading to oocyte retrieval were identified in the National Quality Registry of Assisted Reproduction. Data collected included patient characteristics as well as information about the treatment cycle and pregnancy outcome. The patients were divided into season subgroups, (summer, autumn, winter and spring) based on the date of oocyte retrieval. The primary outcome was live birth rate, which was defined as the number of live births per oocyte retrieval and embryo transfer (ET). Other outcomes included clinical pregnancy per ET and miscarriage per clinical pregnancy. Logistic regression with multiple imputation was performed to evaluate whether there was an association between season and IVF/ICSI outcomes, with summer as reference. Adjustments were made for woman’s age, year of treatment, BMI, total FSH/hMG dose, type of treatment, fertilization type, embryonic stage at ET and number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE Live birth rate per oocyte retrieval ranged between 24% and 26% among seasons. A significantly higher live birth rate was seen for spring compared with summer, 26% versus 24%, respectively (adjusted OR 1.08, 95% CI 1.02-1.16, p=0.02). No significant association was seen when winter and autumn were compared with summer. Live birth rate per ET ranged between 29% and 31% among seasons. A significantly higher live birth rate was seen for spring and autumn compared with summer, at 31% and 31% respectively versus 29% (adjusted OR 1.08, 95% CI 1.01-1.16, p=0.04 and adjusted OR 1.09, 95% CI 1.01-1.16, p=0.02) respectively. No significant association was seen when winter was compared with summer. Clinical pregnancy rate varied between 36% and 38% and miscarriage rate between 16% and 18%, with no significant seasonal associations. LIMITATIONS, REASONS FOR CAUTION Possible limitations are the retrospective design of the study and unmeasured confounders. Another limitation is that a generalized estimating equation (GEE) model was not used. The use of a GEE model would have made it possible to include all started fresh IVF/ICSI cycles since it allows for correction for any dependence between cycles within women. WIDER IMPLICATIONS OF THE FINDINGS The results of this large registry study give no support for the hypothesis that IVF/ICSI treatments performed during summer season, with the highest degree of sunlight and vitamin D synthesis, is associated with higher pregnancy and live birth rates. In fact, our results showed significantly lower live birth rates during summer compared with spring and autumn. However, the magnitude of this difference was small and unlikely of clinical value. We suggest that season should not be taken into consideration when planning and performing fresh IVF/ICSI treatments. STUDY FUNDING/COMPETING INTEREST(S) Financial support was received through the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70 940) and grants from the Hjalmar Svensson's Research Foundation (Grant Nr. HJSV2021019 and HJSV2021037). None of the authors declare any conflict of interest. TRIAL REGISTRATION NUMBER N/A

The role of serum vitamin D in patients with normal ovarian reserve undergoing the first IVF/ICSI cycle

“…Since the production of serum vitamin D mainly depends on the synthesis of cholecalciferol in the skin through sun exposure, the season is an important factor affecting serum vitamin D. It is known that season may have an impact on the natural conception and live birth, one of the main reasons for this is because vitamin D levels increase during summer and autumn (41), but results of the correlation between seasons and ART outcomes are inconsistent. A recently published study even shows that live births are significantly lower in summer compared to spring and autumn, and similar clinical pregnancy probabilities were seen between summer and winter (42). In this study, to avoid seasons from interfering with the multiple outcome analysis, we included the season of blood sampling and the season of ET in the multivariate analysis of embryo development and ET outcomes, respectively.…”

No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study

“…Moreover, clinical evidence from various RCTs indicated that vitamin D supplementation did not improve miscarriage rates as expected ( Tamblyn et al , 2022 ; Zhou et al , 2022 ; Meng et al , 2023 ). Although abundant exposure to ultraviolet radiation during the summer leads to a significant increase in serum vitamin D levels, research has not found any evidence suggesting improved clinical pregnancy rates, live birth rates, or reduced miscarriage rates in women undergoing oocyte retrieval and embryo transfer during the summer ( Carlsson Humla et al , 2022 ). These controversial findings prompted us to investigate the causal relationship between vitamin D and miscarriage, rather than the mere association.…”

Season and temperature do not affect cumulative live birth rate and time to live birth in in vitro fertilization

“…Another study examining frozen embryo transfer cycles reported the interesting finding that summer oocyte retrieval and oocyte retrieval at higher temperatures were associated with higher clinical pregnancy and live birth rates but not with seasonal parameters of frozen transfer day, suggesting that any seasonal effect on IVF success was associated with ovarian function and oocyte quality ( 32 ). In a nationwide, register-based cohort study, live birth rates were significantly higher in spring than in summer ( 39 ). These findings are controversial, however.…”