Study design and patients
This was a consecutive, retrospective cohort study of 1638 cycles undergoing FET between June 2014 and December 2017 in the Center for Assisted Reproductive Technology of Northwest Women’s and Children’s Hospital, China. The selection of the study population was shown in Fig. 1. Women who underwent the first cycle of FET were considered eligible for the study if they were diagnosed with PCOS according to Rotterdam criteria and had previous in vitro fertilization cycles with embryo cryopreservation, regardless of age, diagnosis, embryo stage, or the number of transferred embryos. We excluded patients who were not diagnosed with PCOS and multiple FET cycles.
Propensity Score Matching (Psm)
Given the differences in the baseline characteristics between the two groups, propensity-score matching was used to identify a cohort of women with similar baseline characteristics. A propensity score for endometrial preparation was estimated applying a multivariable logistic regression model, with female age at embryo transfer and BMI as covariates. Matching was performed with the use of a 1:1 matching protocol without replacement, with a caliper width equal to 0.05 of the standard deviation of the logit of the propensity score.
Endometrial Preparation Protocols
Hormone replacement treatment (HRT) cycle Supplementation with oral estrogens (4-6mg/day; Progynova; Bayer Schering Pharma AG, Berlin, Germany) was administered on day 2–5 of the menstrual cycle. Serum progesterone (P) level and ultrasound were performed 10–12 days later. If endometrial thickness > 7 mm and P < 1.5 ng/ml, progesterone was administered, and FET was scheduled. Embryo transfer was performed after 3 days (cleavage stage embryos) or 5 days (blastocyst stage embryos).
GnRHa + HRT cycle GnRHa (3.75mg; Diphereline, Ipsen Pty Ltd, France) was injected on day 2–5 of menstruation. Oral estrogens were administered 30 days after GnRHa and HRT protocol was then performed as previously described.
Luteal Phase Support And Pregnancy Confirmation
600mg of vaginal micronized progesterone (Utrogestan, Besins, Belgium), 30mg oral progesterone (Dupbaston, Abbott Biologicals B.V., Netherlands) daily, and estrogens (the same dosage as endometrial preparation) were given from the day of embryo transfer. All patients were followed up and the pregnancy test with biochemical hCG was performed 14 days after embryo transfer. If serum hCG > 50 IU/L, luteal support continued. Transvaginal ultrasound was performed 5 weeks after embryo transfer to determine the number of gestational sacs and fetal viability.
Definition Of Clinical Outcomes
According to the ASRM consensus published in 2017, the definition of clinical outcomes was confirmed [7]. Clinical pregnancy was defined as an intrauterine gestational sac and fetal heart motion diagnosed by ultrasonographic visualization. Preterm birth was defined as a birth that occurs before 37 weeks of gestation. Ectopic pregnancy was defined as a gestational sac observed by ultrasound outside the uterine cavity. Miscarriage was defined as a pregnancy loss before 24 weeks. Live birth was defined as the delivery of any viable neonate beyond 24 weeks of gestation. All the patients were followed up until one year after embryo transfer.
Statistical analysis
Data are presented as mean ± SD for continuous variables and as n (%) for categoric variables. Counts and proportions were used for the categorical variables. One-way analysis of variance was used for continuous variables, and the Pearson'sχ2 test was used for categorical variables with Fisher's exact test when necessary. Logistic regression, presented as unadjusted odds ratio (crude odds ratio (OR)) or adjusted odds ratio (aOR) with 95% confidence interval (CI) with the 95% of confidence interval (CI), was performed. A variance inflation factor (VIF) was calculated to test for collinearity among the predictors. We adjusted for covariates that, when added to this model, changed the matched odds ratio by at least 10 percent in the multivariable regression analyses. In the adjusted model: we adjusted female age at embryo transfer, female age at oocyte retrieval, infertility duration, infertility type, cause of infertility, AFC, BMI, endometrial thickness, duration of endometrial preparation, triple-line endometrial pattern, protocol in the fresh cycle, Gn duration, Gn dosage, no. of oocyte retrieved, no. of transferred embryos, no. of available embryos, no. of good quality embryos transferred, embryo stage and fertilization type. Data were analyzed using the statistical packages R (The R Foundation; http://www.r-project.org;version 3.4.3) and Empower (R) (www.empowerstates.com, X&Y solutions, inc. Boston, Massachusetts). The level of significance was set at p < 0.05.