Jinliang Zhu1, Xinjie Zhuang1, Lixue Chen1, Ping Liu2, Jie Qiao2. 1. Department of Obstetrics and Gynecology, Reproductive Medical Center, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China. 2. Department of Obstetrics and Gynecology, Reproductive Medical Center, Peking University Third Hospital, Beijing, China Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China bysylp@sina.com jie.qiao@263.net.
Abstract
STUDY QUESTION: Does embryo culture medium influence the percentage of males at birth? SUMMARY ANSWER: The percentage of males delivered after ICSI cycles using G5™ medium was statistically significantly higher than after cycles where Global, G5™ PLUS, and Quinn's Advantage Media were used. WHAT IS KNOWN ALREADY: Male and female embryos have different physiologies during preimplantation development. Manipulating the energy substrate and adding growth factors have a differential impact on the development of male and female embryos. STUDY DESIGN, SIZE AND DURATION: This was a retrospective analysis of the percentage of males at birth, and included 4411 singletons born from fresh embryo transfer cycles between January 2011 and August 2013 at the Center for Reproductive Medicine of Third Hospital Peking University. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Only singleton gestations were included. Participants were excluded if preimplantation genetic diagnosis, donor oocytes and donor sperm were used. The database between January 2011 and August 2013 was searched with unique medical record number, all patients were present in the database with only one cycle. Demographics, cycle characteristics and the percentage of male babies in the four culture media groups were compared with analysis of variance or χ(2) tests. Multivariable logistic regression was done to determine the association between the sex at birth and culture media after adjusting for other confounding factors, including parental age, parental BMI, type of infertility, parity, number of embryos transferred, number of early gestational sacs, cycles with testicular sperm aspiration (TESA)/percutaneous epididymal sperm aspiration (PESA)/testicular sperm extraction (TESE), number of oocytes retrieved, cycles with blastocyst transfers, and gestational age within ICSI group. MAIN RESULTS AND THE ROLE OF CHANCE: Within the IVF group, the percentage of males at birth for G5™, Global, Quinn's and G5™ PLUS media were comparable (P > 0.05); however, within the ICSI group, the percentage of male babies in cycles using G5™(56.1%) was statistically significantly higher than in cycles that used Global (47.2%; P = 0.003), G5™ PLUS (47.7%; P = 0.005) or Quinn's media (45.0%; P = 0.009). There were no statistically significant differences in the percentage of males at birth between cycles that used Global, G5™ PLUS and Quinn's media (P > 0.05). Multivariable logistic regression indicated that culture media (G5™ versus Global, G5™ PLUS, and Quinn's) were significantly associated with the sex at birth (P = 0.008) after adjusting for parental age, parental BMI, type of infertility, parity, number of embryos transferred, number of early gestational sacs, cycles with TESA/PESA/TESE, number of oocytes retrieved, cycles with blastocyst transfers, and gestational age. LIMITATIONS AND REASONS FOR CAUTION: This study was not a randomized controlled trial and allocation of treatment cycles over the four media was not completely at random. Cigarette smoking was not included in the current study because this confounding factor was not registered in our database. Moreover, intra-variability of sperm selection between the five embryologists may directly affect the percentage of males. WIDER IMPLICATIONS OF THESE FINDINGS: Our study suggests that human embryogenesis responds differently to G5™, Global, G5™ PLUS and Quinn's Advantage Medium. This finding can be generalized to other commercial culture media. STUDY FUNDING/COMPETING INTERESTS: National Natural Science Foundation of China for Young Scholars (81300483 and 81200466). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.
STUDY QUESTION: Does embryo culture medium influence the percentage of males at birth? SUMMARY ANSWER: The percentage of males delivered after ICSI cycles using G5™ medium was statistically significantly higher than after cycles where Global, G5™ PLUS, and Quinn's Advantage Media were used. WHAT IS KNOWN ALREADY: Male and female embryos have different physiologies during preimplantation development. Manipulating the energy substrate and adding growth factors have a differential impact on the development of male and female embryos. STUDY DESIGN, SIZE AND DURATION: This was a retrospective analysis of the percentage of males at birth, and included 4411 singletons born from fresh embryo transfer cycles between January 2011 and August 2013 at the Center for Reproductive Medicine of Third Hospital Peking University. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Only singleton gestations were included. Participants were excluded if preimplantation genetic diagnosis, donor oocytes and donor sperm were used. The database between January 2011 and August 2013 was searched with unique medical record number, all patients were present in the database with only one cycle. Demographics, cycle characteristics and the percentage of male babies in the four culture media groups were compared with analysis of variance or χ(2) tests. Multivariable logistic regression was done to determine the association between the sex at birth and culture media after adjusting for other confounding factors, including parental age, parental BMI, type of infertility, parity, number of embryos transferred, number of early gestational sacs, cycles with testicular sperm aspiration (TESA)/percutaneous epididymal sperm aspiration (PESA)/testicular sperm extraction (TESE), number of oocytes retrieved, cycles with blastocyst transfers, and gestational age within ICSI group. MAIN RESULTS AND THE ROLE OF CHANCE: Within the IVF group, the percentage of males at birth for G5™, Global, Quinn's and G5™ PLUS media were comparable (P > 0.05); however, within the ICSI group, the percentage of male babies in cycles using G5™(56.1%) was statistically significantly higher than in cycles that used Global (47.2%; P = 0.003), G5™ PLUS (47.7%; P = 0.005) or Quinn's media (45.0%; P = 0.009). There were no statistically significant differences in the percentage of males at birth between cycles that used Global, G5™ PLUS and Quinn's media (P > 0.05). Multivariable logistic regression indicated that culture media (G5™ versus Global, G5™ PLUS, and Quinn's) were significantly associated with the sex at birth (P = 0.008) after adjusting for parental age, parental BMI, type of infertility, parity, number of embryos transferred, number of early gestational sacs, cycles with TESA/PESA/TESE, number of oocytes retrieved, cycles with blastocyst transfers, and gestational age. LIMITATIONS AND REASONS FOR CAUTION: This study was not a randomized controlled trial and allocation of treatment cycles over the four media was not completely at random. Cigarette smoking was not included in the current study because this confounding factor was not registered in our database. Moreover, intra-variability of sperm selection between the five embryologists may directly affect the percentage of males. WIDER IMPLICATIONS OF THESE FINDINGS: Our study suggests that human embryogenesis responds differently to G5™, Global, G5™ PLUS and Quinn's Advantage Medium. This finding can be generalized to other commercial culture media. STUDY FUNDING/COMPETING INTERESTS: National Natural Science Foundation of China for Young Scholars (81300483 and 81200466). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.