Risk factors associated with preterm birth after IVF/ICSI

Ethics, inclusion and exclusion criteria, data collection

The study was approved by the ethics committee of Reproductive & Genetic Hospital of Citic-Xiangya, Changsha, China (approval document number: LL-SC-2019-003). A total of 4349 infertile women who had undergone IVF/ICSI treatment and obtained live birth in the Reproductive & Genetic Hospital of Citic-Xiangya from January 1st, 2016 to December 30th, 2017 were enrolled.

Inclusion criteria were as follows:

  1. (a)

    Women treated with super-ovulation protocols exactly as described previously 9

  2. (b)

    Fresh embryo transfer recipients, who received IVF/ICSI treatment

  3. (c)

    Giving live birth after ART

Exclusion criteria were as follows:

  1. (a)

    Using donor sperms or donor eggs for ART

  2. (b)

    Complete clinical data were not available

  3. (c)

    Post-term birth (> 42nd week of gestation) cases were excluded

  4. (d)

    Infertile couples with known female or male genetic causes of infertility

Gestational age was calculated by adding 2 weeks (14 days) to the number of days since fertilization10. Note: Gestational age was determined as the 17th day of gestation when a 6–8 cell embryo was transferred into the uterus and as the 19th day of gestation when a blastocyst was transferred.

Full-term birth was defined as a live birth with a gestational age between 37 but not over 42 weeks (37 weeks ≤ gestational age < 42 weeks). Preterm birth was defined as a live birth with a gestational age of at least 20 but not over 37 weeks (20 weeks ≤ gestational age < 37 weeks)11. Early preterm birth was defined as a live birth with a gestational age between 20 but not over 32 weeks (20 weeks ≤ gestational age < 32 weeks)12.

All patient’s data (clinical data as well as laboratory data) used in our study were extracted from the routine electronic patient records used in our hospital.

Clinic data collection

Informed consent was obtained from all subjects and/or their legal guardian(s). A structured medical history was taken. The following risk factors for preterm birth were examined in this study:

Maternal risk factors: (1) basic parameters before super-ovulation: nationality, education, age, body height, body weight, infertility duration, types of infertility, causes of infertility (maternal causes, paternal causes, maternal and paternal causes, unknown causes), blood pressure readings. (2) Pregnancy history: parity, artificial abortion, drug abortion, spontaneous abortion, ectopic pregnancy, number of deliveries, vaginal delivery, cesarean section (3) blood test result before super-ovulation: liver and kidney function, lipid items, blood coagulation function. (4) Pregnancy related factors: multiple pregnancy, embryo reduction, gestational diabetes, gestational hypertension, placenta previa.

Relevant risk factors during IVF/ICSI procedure: cycle count, fertilization way, embryo transfer type (blastocyst or cleavage stage embryo transfer), ovulation induction scheme, source of sperm, transferred embryo count, dosage of gonadotropin, ovulation inducing days.

Offspring data: gestational age at delivery, gender, birth weight.

Basic parameters about the mother, pregnancy history, gynecological complications, and relevant risk factors during IVF/ICSI procedure came from the case report in the hospital. Furthermore, blood test results from maternal blood taken before the beginning of superovulation was extracted from the case report. Pregnancy related factors and offspring data were followed up strictly by a special nurse.

Patient and public involvement

This study is a retrospective study. Data were obtained through the electronical medical record system of the hospital. Patients were not directly involved in this study. The patients were unaware of the results of the study.

Statistical analysis

Continuous variables are represented as mean ± SD for normally distributed variables and student’s unpaired t-test was used for comparison of variables between two groups. Continuous variables are represented as median and quartiles M (Q1 − Q3) for non-normally distributed variables and Mann–Whitney nonparametric test was used for comparison of variables between groups. Categorical variables are described as frequency and percentages. Pearson’s chi-square test was used for testing qualitative data and Fisher’s exact test was used when the expected frequencies were < 5%.

Multivariate logistic regression analyses with step forward selection using the likelihood method were applied to examine the association between the patient’s characteristics and the risk of preterm brith. Analyzed variables with P < 0.05 in the univariate analysis were entered into the multivariate analysis. No other factors were considered as confounders. Results are represented as ORs with corresponding 95% CIs and P values.

Statistical package for social sciences (SPSS version 22.0, Chicago, IL, USA) was used to perform all data analyses and a two-sided P value < 0.05 was considered to be statistically significant.

All methods were carried out in accordance with relevant guidelines and regulations of the People Republic of China.

Ethics approval

This study was approved by the ethics committee of the Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China (approval number: ll-sc-2019-003). The data of this study is only used for this study, and the data of patients are strictly confidential. This study will not cause any harm to the patients’ body and mind.