To investigate clinical outcomes and safety of the early follicular phase prolonged protocol and gonadotropin-releasing hormone antagonist (GnRH-A) protocol of patients with expected high ovarian response.

A retrospective cohort analysis of the expected high ovarian response patients during in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) was performed in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from September 2015 to May 2019, including 1855 gonadotropin-releasing hormone agonist (GnRH-a) cycles and 720 GnRH-A cycles. The main outcome measures were the clinical outcomes, the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS), the pregnancy outcome of the first cycle of whole embryo freezing, cumulative pregnancy rate per oocytes retrieval cycle and time to pregnancy (TTP). And a self-controlled study was performed to compare the clinical outcomes of the patients who underwent early follicular phase prolonged protocol previously and underwent GnRH-A protocol or early follicular phase prolonged protocol later.

1) There was no statistical difference between GnRH-a group and GnRH-A group in maternal age, body mass index (BMI), basal follicle-stimulating hormone (bFSH), anti-Müllerian hormone (AMH) and intima thickness on the human chorionic gonadotropin (hCG) trigger day (P>0.05). Compared with the Gn start-up [(170.12±53.94) IU], No. of obtained oocytes (20.60±9.92), No. of available embryos (10.96±6.59), and No. of high-quality embryos (6.47±4.97) in the GnRH-A group, the gonadotropins (Gn) start-up [(135.11±36.61) IU], No. of obtained oocytes (17.79±7.80), No. of available embryos (9.08±5.56), and No. of high-quality embryos (5.18±4.56) in the early follicular phase prolonged protocol group were significantly reduced correspondingly (P<0.001,P<0.001,P<0.001,P=0.012), while Gn used duration [(14.3±3.23) d], total Gn used dosage [(2 322.08±1 020.48) IU], incidence of moderate to severe OHSS after hCG trigger (9.54%) and fresh cycle clinical pregnancy rate (69.44%) increased significantly (P<0.001). 2) The clinical pregnancy rate and the abortion rate of the first cycle of whole embryo freezing were not statistically different between the two groups (P>0.05). 3) There was no statistically significant difference in the cumulative pregnancy rate between the two groups (P>0.05); the TTP of GnRH-A after fresh embryo transfer [(47.67±3.18) d] and frozen embryo cycle [(140.33±45.43) d] were significantly less than those in the early follicular phase prolonged protocol group [(81.25±3.72) d, (185.19±46.52) d,P<0.001]. But there was no significant difference in TTP between the two groups in the total transplantation period (P>0.05). 4) The comparison of early follicular phase prolonged protocol and GnRH-A protocol self-control showed that No. of available embryos (5.79±3.14) and No. of high-quality embryos (2.78±1.50) in early follicular phase prolonged protocol were significantly lower than those in GnRH-A group (10.14±4.74, 5.70±3.50) (P=0.027, P=0.005), and the total Gn used dosage [(2 535.80±1 212.17) IU] and moderate to severe OHSS incidence rate (4.55%) were significantly higher (P=0.049, P=0.043). 5) The comparison of early follicular phase prolonged protocol and self-control of early follicular phase prolonged protocol protocol again showed that the BMI assisted by the early follicular phase prolonged protocol again [(24.63±2.99) kg/m²] was lower than that of the early follicular phase prolonged protocol in the first cycle [(25.01±3.12) kg/m², P=0.049], while the No. of high-quality embryos (4.00±3.58) and the clinical pregnancy rate of early follicular phase prolonged protocol again (52.10%) were significantly higher than those of the first cycle (2.56±2.12, 29.41%) (P=0.046, P=0.004).

For patients with high expected response, the GnRH-A protocol can significantly reduce the duration of Gn used, the dosage of Gn used and the incidence of moderate to severe OHSS, increase the No. of oocytes, the No. of available embryos and the No. of high-quality embryos. The clinical pregnancy rate of the fresh cycle was lower in GnRH-A protocol, and whole embryo freezing can be considered. For the previous early follicular phase prolonged protocol patients, GnRH-A protocol can be considered next time, and the early follicular phase prolonged protocol can be selected again based on improvement of the basic state and prevention of OHSS.

Early follicular phase prolonged protocol; Gonadotropin-releasing hormone antagonist protocol; Clinical pregnancy; Ovarian hyperstimulation syndrome; Cumulative pregnancy rate; Time to pregnancy