Secondary sex ratio in assisted reproduction: an analysis of 1 376 454 treatment cycles performed in the UK

Abstract

STUDY QUESTION Does ART impact the secondary sex ratio (SSR) when compared to natural conception? SUMMARY ANSWER IVF and ICSI as well as the stage of embryo transfer does impact the overall SSR. WHAT IS KNOWN ALREADY The World Health Organization quotes SSR for natural conception to range between 103 and 110 males per 100 female births. STUDY DESIGN, SIZE, DURATION A total of 1 376 454 ART cycles were identified, of which 1 002 698 (72.8%) cycles involved IVF or ICSI. Of these, 863 859 (85.2%) were fresh cycles and 124 654 (12.4%) were frozen cycles. Missing data were identified in 14 185 (1.4%) cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS All cycles recorded in the anonymized UK Human Fertilisation and Embryology Authority (HFEA) registry database between 1991 and 2016 were analysed. All singleton live births were included, and multiple births were excluded to avoid duplication. MAIN RESULTS AND THE ROLE OF CHANCE The overall live birth rate per cycle for all IVF and ICSI treatments was 26.2% (n = 262 961), and the singleton live birth rate per cycle was 17.1% (n = 171 399). The overall SSR for this study was 104.0 males per 100 female births (binomial exact 95% CI: 103.1–105.0) for all IVF and ICSI cycles performed in the UK recorded through the HFEA. This was comparable to the overall SSR for England and Wales at 105.3 males per 100 female births (95% CI: 105.2–105.4) from 1991 to 2016 obtained from the Office of National Statistics database. Male predominance was seen with conventional insemination in fresh IVF treatment cycles (SSR 110.0 males per 100 female births; 95% CI: 108.6–111.5) when compared to micro-injection in fresh ICSI treatment cycles (SSR 97.8 males per 100 female births; 95% CI: 96.5–99.2; odds ratio (OR) 1.16, 95% CI 1.12–1.19, P < 0.0001), as well as with blastocyst stage embryo transfers (SSR 104.8 males per 100 female births; 95% CI: 103.5–106.2) when compared to a cleavage stage embryo transfer (SSR 101.2 males per 100 female births; 95% CI: 99.3–103.1; OR 1.03, 95% CI 1.01–1.06, P = 0.011) for all fertilization methods. LIMITATIONS, REASONS FOR CAUTION The quality of the data relies on the reporting system. Furthermore, success rates through ART have improved since 1991, with an increased number of blastocyst stage embryo transfers. WIDER IMPLICATIONS OF THE FINDINGS This is the largest study to date evaluating the impact of ART on SSR. The results demonstrate that, overall, ART does have an impact on the SSR when assessed according to the method of fertilization (ICSI increased female births while IVF increased males). However, given the ratio of IVF to ICSI cycles at present with 60% of cycles from IVF and 40% from ICSI, the overall SSR for ART closely reflects the population SSR for, largely, natural conceptions in England and Wales. STUDY FUNDING/COMPETING INTEREST(S) The study received no funding. C.M.B. is a member of the independent data monitoring group for a clinical endometriosis trial by ObsEva. He is on the scientific advisory board for Myovant and medical advisory board for Flo Health. He has received research grants from Bayer AG, MDNA Life Sciences, Volition Rx and Roche Diagnostics as well as from Wellbeing of Women, Medical Research Council UK, the NIH, the UK National Institute for Health Research and the European Union. He is the current Chair of the Endometriosis Guideline Development Group for ESHRE and was a co-opted member of the Endometriosis Guideline Group by the UK National Institute for Health and Care Excellence (NICE). I.G. has received research grants from Wellbeing of Women, the European Union and Finox. TRIAL REGISTRATION NUMBER Not applicable.

Developmental Plasticity in Response to Embryo Cryopreservation: The Importance of the Vitrification Device in Rabbits

“…Thus, female embryos seemed more sensitive to the vitrification conditions, as skewed sex ratio towards male gender was detected at birth. This phenomenon has been well established among ART births, which has been related with abnormal inactivation in one of the two X chromosomes in females and a higher rate of irregular placentation that incurs higher mortality for female embryos [33][34][35][36]. However, in the field of embryo cryopreservation, information is limited and controversial, and changes in the sex ratio have been attributed to the grading criteria used, instead of to the cryopreservation procedure per se [37][38][39].…”

Associated factors of secondary sex ratio of offspring in assisted reproductive technology: a cross-sectional study in Jilin Province, China

“…As far we know, the normal value of SSR is 51.22% [ 1 ]. Different from those of large sample studies, an analysis from the UK showed that the SSR of babies born through ART was 50.98% [ 11 ]. It was lower than the normal value and approximated to ours.…”

Differences in pregnancy complications and outcomes by fetal gender among Japanese women: a multicenter cross-sectional study

“…Maternal age, maternal height, pre-pregnancy BMI, parity, conception method, and smoking status during pregnancy were considered potential confounding factors in the multivariate analysis. Although some studies have shown that sex selection may be influenced by environmental factors, such as the conception method 21 and maternal periconceptional smoking status 22 , there is a lack of studies on significant associations between maternal factors (such as maternal age, height, and BMI) and fetal sex. However, we considered that the adjustment of these factors was important as there is insufficient evidence showing that they are independent of fetal sex.…”