Assessing the Pregnancy Protective Impact of Scheduled Nonadherence to a Novel Progestin-Only Pill: Protocol for a Prospective, Multicenter, Randomized, Crossover Study (Preprint)

Abstract

BACKGROUND Oral contraceptives are the most widely used hormonal contraceptive methods in the United States. Progestin-only pills (POP) are commonly reserved for women with medical co-morbidities but in actuality, POPs can be safety used by anyone wanting to prevent pregnancy. This wide safety profile makes them an ideal candidate for being available over-the-counter without a prescription. However for users to best understand pill-taking instructions, we need a better understanding of the ability of POPs to prevent pregnancy when adherence issues occur in the form of a missed or delayed pill. OBJECTIVE To determine the impact of the POP containing norgestrel 75 mcg on cervical mucus and ovarian activity as well as levonorgestrel levels during a treatment period of typical and non-perfect adherence. METHODS This prospective, multi-center, randomized, cross-over study assesses the effect of norgestrel 75 mcg (Opill®) on cervical mucus and ovarian activity during reported compliant daily use, after a 6-hour delayed intake mid-cycle, and after a mid-cycle missed pill. Subject participation will be approximately 4.5 months long including up to 1 month for screening, three 28-day treatment cycles, and 2 weeks for follow up and end of study processes. We will recruit at two US sites: Oregon Health & Science University, Portland, Oregon and University of California Davis Health, Sacramento, California. Reproductive-aged subjects with regular menstrual cycles (21-35 days), body mass index less than 32kg/m2 and proven ovulation [screening luteal phase progesterone > 3 ng/mL (>10 nmol/L)] are eligible to enroll. Participants cannot be at risk for pregnancy during the study period and not use other hormonal methods (e.g. heterosexual abstinence, using barrier or permanent contraception). Norgestrel 75mcg will be taken at the same time daily except for one specific day in each of treatment periods 2 and 3, when the pill will be taken either 6 hours late (delayed pill) or omitted completely (missed pill). Every 3-4 days, we will monitor subjects for follicular activity with transvaginal ultrasound (TVUS) examination, cervical mucus and blood sampling for progesterone (P4), estradiol (E2), FSH, LH. Subjects will undergo serial cervical mucus sampling on the days with missed and delayed pill intake at 8 hours after pill intake on the day before the delayed or missed pill, 3 hours following the scheduled time of pill intake if intake was delayed and six hours after the scheduled time if intake was omitted, and on the next day 30 minutes before the time of scheduled pill intake. Women will also have additional daily visits, for a maximum of 3 visits, if an ovarian follicle >15 mm is observed on TVUS examination. The primary objective of the study is to determine the effect of a delayed intake of 6 hours or of a missed pill on cervical mucus characteristics based on a modified Insler score compared to cervical mucus score during reported daily use of norgestrel 75 mcg. RESULTS Protocol submission. No results CONCLUSIONS Protocol submission. No conclusion CLINICALTRIAL NCT03585712