Data source and variables
This was a retrospective cohort study that used the ART databases from two affiliated hospitals of Peking University (Peking University Third Hospital and Peking University Shenzhen Hospital). 24,422 frozen-thawed embryo transfer (FET) cycles recorded from January 2015 to May 2018 were selected to generate the research database. The database included the following; maternal characteristics (maternal age at treatment, height, weight, infertility type, cause of infertility and duration of infertility, and number of previous ART cycles), treatment records of the current cycle (type of fertilization in the current cycle, numbers of embryo transferred, days of embryo development), maternal outcomes (biochemical pregnancy, clinical pregnancy, monozygotic twins, miscarriages, and maternal complications) and neonatal outcomes (live births, number of live births, gestational age at delivery, birth weight, and congenital malformations).
Of the 24,422 FET cycles, 440 preimplantation genetic analysis (PGA) cycles, 42 in vitro maturation (IVM) cycles, 3 assisted oocyte activation (AOA) cycles, 13 cycles with missing values in numbers of embryo transferred, 6 cycles with missing values in days of embryo development, 20 cycles with two embryos in different development days and 172 cycles with loss to follow-up were excluded from the analysis. Finally, 23,726 cycles were included for the final analysis. This included 13,767 cleavage-stage embryo transfer cycles (58.0%) and 9,959 blastocyst-stage embryo transfer cycles (42.0%). Based on the stage (cleavage-stage or blastocyst-stage) and number (one or two) of embryos transferred, all the selected cycles were divided into four exposure groups: the single cleavage-stage embryo transfer group (C-1) (763 cycles, 3.2%), double cleavage-stage embryo transfer group (C-2) (13004 cycles, 58.0%), single blastocyst-stage embryo transfer group (B-1) (7913 cycles, 33.4%) and double blastocyst-stage embryo transfer group (B-2) (2046 cycles, 8.6%). (Figure 1)
The following data were analyzed for each cycle: maternal age (20-29 years, 30-34 years, 35-37 years, 38-39 years, 40-42 years, or >42 years), body mass index (BMI) (equal to height/weight2 (m/kg2), BMI<18.5 defined as ‘underweight’, 18.5≤BMI<24 defined as ‘fitting’, 24≤BMI<27 defined as ‘overweight’, or BMI≥27 defined as ‘obesity’), infertility type (primary infertility, or secondary infertility), cause of infertility (tubal, ovulatory, endometriosis, male factor, or unexplained), duration of infertility (≤4 years or >4 years), type of fertilization in the current cycle (IVF, ICSI, or IVF+ICSI), previous ART cycles (0-1 cycles, 2-3 cycles, 4-5 cycles, or ≥6 cycles), biochemical pregnancy (yes or no), clinical pregnancy (yes or no), monozygotic twins (yes or no), miscarriage (yes or no), maternal complications (yes or no), live birth (yes or no), twin birth (yes or no), preterm birth (defined as ‘gestational week at delivery <37 weeks, yes or no), low birth weight (defined as ‘birth weight at delivery <2500 grams’, yes or no), small for gestational age infant (SGA, defined as ‘birth weight at delivery <10th percentile for the baby’s gender and gestational age, using Chinese reference charts’3, yes or no), and congenital malformations (yes or no). With regards to cycles with multiple pregnancies or births, the cycle was defined as “yes” for live births, preterm births, low birth weights, SGA or congenital malformations.
The study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (IRB00006761-M2019107).