A comparative study between oral contraceptive long protocol and mid-luteal long protocol in infertility patients with normal ovarian function in in vitro fertilization/intracytoplasmic sperm injection cycles

Objective To explore the effect of oral contraceptive (OC) long protocol and mid-luteal long protocol on ovarian stimulation and clinical outcomes in infertility patients with normal ovarian function in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods The data of 4 677 IVF/ICSI cycles of infertility patients with normal ovarian function were analyzed. Adjusted by age ≤35 years group and >35 years group, the patients who had no ovarian detection or had no spontaneous ovulation received OC long protocol (2 762 cycles, OC group), and the patients who had spontaneous ovulation received the mid-luteal long protocol (1 915 cycles, mid-luteal group). The clinical and laboratory related indicators of different age group were compared between the two ovarian stimulating protocols. Results 1) The levels of estradiol (E2)[≤35 years group: (24.63±10.62) ng/L, >35 years group: (24.24±10.40) ng/L] and luteinizing hormone (LH)[≤35 years group: (0.92±0.59) IU/L, >35 years group: (0.82±0.66) IU/L] on gonadotropin (Gn) starting day in the OC group were less than those in the mid-luteal group [≤35 years group: (25.89±12.80) ng/L, >35 years group: (25.71±10.93) ng/L; ≤35 years group: (1.37±0.59) IU/L, >35 years group: (1.01±0.70) IU/L](P 35 years group: (3 597.5±2 160.4) ng/L] and embryo frozen rate as result from OHSS (≤35 years group: 9.1%, >35 years group: 10.2%) in the OC group were higher than those in the mid-luteal group [≤35 years group: (3 850.8±2 092.4) ng/L, >35 years group: (3 213.4±1 804.5) ng/L; ≤35 years group: 4.9%, >35 years group: 5.9%](P 35 years group: (10.47±2.38) mm] in the OC group was less than that in the mid-luteal group [≤35 years group: (11.62±2.43) mm, >35 years group: (11.09±2.68) mm](P 35 years group) were higher than those in the mid-luteal group [(3 516.9±1 156.1) IU, (12.4±2.2) d](P 35 years group: 25.5%) and clinical pregnancy rate (≤35 years group: 55.7%, >35 years group: 37.5%) in the OC group were less than those in the mid-luteal group (≤35 years group: 46.7%, >35 years group: 31.4%; ≤35 years group: 65.6%, >35 years group: 46.9%)(P<0.05). Conclusions 1) Infertility patients with normal ovarian function underwent OC long protocol might lead to over pituitary suppression. Especially, patients aged >35 years old who underwent OC long protocol should be increased dosage and duration of Gn therapy to achieve similar ovarian stimulation of the mid-luteal long protocol. 2) Infertility patients with normal ovarian function underwent OC long protocol received less implantation rate and clinical pregnancy rate that are relevant to endometrial thickness and endometrial receptivity. 3) The higher level of E2 on hCG injection day, the higher embryo frozen rate of OHSS. Therefore, infertility patients with normal ovarian function choose the mid-luteal long protocol as far as possible, and avoid using OC. Key words: In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI); Oral contraceptive (OC) long protocol; Mid-luteal long protocol