Combined oral contraceptives (OCs) are commonly taken for 14 to 28 days prior to GnRH analogues to ease cycle scheduling, synchronize follicular development, further prevent LH surges, reduce the incidence of ovarian cysts, and reduce cancellation rates resulting from hyperstimulation (331,337,338). Patients can begin OCs anytime between days 1 and 5 of menses (337). For antagonist cycles, COH begins 2 to 5 days after stopping OCs (irrespective of menses) (331). During long GnRH agonist protocols, the agonist overlaps the final 5 days of OC use, followed by initiation of COH on the second or third day of withdrawal bleeding (300,338). As previously discussed, microdose ﬂare protocols involve pretreatment with 14 to 21 days of OC, followed 4 days later by a microdose of agonist. COH typically starts 1 to 2 days later (324).
The progestins norethindrone acetate 10 mg orally daily, medroxyprogesterone acetate 10 mg orally daily, or a single intramuscular dose of progesterone (not specified) can be used in place of an OC in ART cycles, but recommendations on the duration of treatment and the timing of initiation vary widely: a duration of 5 to 20 days and initiation anytime between days 1 and 19 of menses have been reported. A dose of 4 mg of daily micronized 17β estradiol or estradiol valerate has been used in lieu of OCs in ART cycles, with initiation between cycle days 15 and 21 and a duration of 10 to 15 days. Although OC pretreatment for antagonist cycles has been shown to increase both the duration of stimulation and the amount of medication used, its effect on pregnancy rates is controversial (331,337). OC pretreatment during GnRH agonist cycles is associated with higher pregnancy rates than those in cycles without pretreatment (300). Progestin and estradiol pretreatment do not affect live birth rates in either agonist or antagonist cycles (337).
Prenatal vitamins should be given to all infertility patients beginning at least 1 month prior to initiation of infertility treatment. Although aspirin is commonly used during IVF regimens, recent studies have failed to demonstrate beneficial changes in pregnancy rates (339,340). Antimicrobial prophylaxis using doxycycline or azithromycin for both partners is often given during ART cycles, particularly those involving assisted hatching procedures, although these medications have not been clearly associated with improved pregnancy rates (287,289,341). Glucocorticoids given to women during the peri-implantation period may improve pregnancy rates in women with autoimmune disease, those undergoing assisted hatching or frozen/thaw embryo transfers, and in women of advanced maternal age (341). Metformin may limit ovarian hyperstimulation (OHSS) in PCOS patients, but shows no benefit for pregnancy or live birth rates (342).