Mechanism of action of a 0.075 mg norgestrel progestogen-only pill 2. Effect on cervical mucus and theoretical risk of conception

Objective: To evaluate the cervical mucus effects of a norgestrel 0.075 mg progestin-only contraceptive pill over a 28-day cycle. Study Design: We recruited persons ages 18 to 35 with normal cycles at 2 US academic medical centers. Participants took norgestrel 0.075 mg daily for 28 days at the same time (within a 3 hour window) daily, recorded through a text-message based e-diary. We extracted cervical mucus using a standardized aspiration technique on the day of pill initiation and then at least every 3 to 4 days over the cycle. We monitored subjects for follicular activity with transvaginal ultrasound examination and blood sampling for ovarian hormones and gonadotropins at each visit. We assessed cervical mucus scoring using a 4-category/12-point modified Insler scale (score ≥9 [favoring fertility], 5–8 [intermediate], and ≤4 [unfavorable to fertility]). We stratified cervical mucus scores by serum estradiol levels and ovulatory status based on a modified Hoogland score. Results: Excluding enrollment, we collected and evaluated 413 mucus samples from 51 participants. Participants had a median mucus score of 0 (Interquartile Range 0, 2); most had scores ≤4 (samples = 385, 93%) and none had a score ≥9 favoring fertility. Seventeen (33%) participants ovulated, of which 14 (82%) had unfavorable mucus scores (≤4) at the time of ovulation and 3 (18%) had intermediate scores (5-8). Conclusions: Norgestrel 0.075 mg daily prevents mucus changes that favor fertility, even during ovulatory cycles. Implications: Daily administration of norgestrel 0.075 mg over an initial 28-day cycle did not result in fertile cervical mucus. Although approximately one-third of users ovulated in this first cycle of pill use, contraceptive efficacy may be maintained by mucus effects.