K.T. Barnhart

The pharmacology of methotrexate

Ectopic pregnancy (EP) is a major cause of maternal morbidity and mortality. The treatment of this condition is primarily surgical, but medical management in selected cases is safe, effective, cost-effective and eliminates the morbidity of surgery. Methotrexate (MTX) is a folate antagonist that can be used for non-oncologic purposes including the treatment of EP. The dose and duration of MTX therapy for EP is much lower than that used in oncology cases, thus reducing side effects and increasing safety. MTX selectively acts on rapidly dividing cells, such as trophoblast cells which comprise the implantation site of the early gestation. The two most common methods of administering MTX to patients with EP are im. administration of a single-dose, based on body surface area and calculated by the equation 50 mg/m2 (without the need for leucovorin rescue), or the multiple-dose regimen of 1 mg/kg of MTX, alternating with 0.1 mg/kg of leucovorin rescue. Both methods have a similar side effect profile, resulting in the rare occurrence of nausea, vomiting, stomatitis, elevated liver function tests, anorexia and diarrhoea. The two methods yield success rates similar to those of conservative surgical therapy with similar future fertility. The potential single- and multi-dose methods have never been directly compared, but it appears that the success of multiple dosing is more effective. As the efficacy of MTX therapy is not 100%, women must be followed clinically until there is compete resolution of human Chorionic Gonadotropin (hCG) titers from their serum.

Return to fertility following discontinuation of oral contraceptives.

OBJECTIVESnTo provide an overview of the studies that have evaluated the return to fertility following cessation of oral contraceptives (OCs), including recent evidence in women discontinuing extended-cycle and continuous-use regimens.nnnDESIGNnComprehensive review.nnnPATIENT(S)nNone.nnnINTERVENTION(S)nRelevant articles were identified through a PubMed literature search (1960-2007) and a cross-reference of published data.nnnMAIN OUTCOME MEASURE(S)nTime to fertility following contraceptive use.nnnRESULT(S)nNumerous studies have demonstrated some delay in the time to conception in previous users of OCs who discontinued use in order to conceive, but this impairment appears to be temporary and typically limited to the early months following cessation of OC use. Reported 12-month conception rates in former cyclic OC users range from 72%-94% and are similar to those observed in women discontinuing intrauterine devices (71%-92%), progestin-only contraceptives (70%-95%), condoms (91%), and natural family planning (92%). There is a limited amount of data on the time to conception in women stopping extended-cycle and continuous-use OCs, but the data suggest that subsequent return to fertility is generally comparable to that of cyclic OCs.nnnCONCLUSION(S)nA comprehensive survey of reported data indicates that the return of fertility in former OC users (both cyclic and extended/continuous regimens) in women who stop use in order to conceive is comparable to that observed with other contraceptive methods.

Lifestyle and environmental risk factors for infertility

Environmental and lifestyle factors interact with human reproduction and are potentially modifiable. This review addresses the available evidence for the role of cigarette smoking, alcohol use, caffeine use, cocaine use, marijuana use, obesity and circadian rhythm in fertility. Clinical studies in this field have many methodological limitations. Based on current evidence, we advise against cigarette smoking, alcohol use, high caffeine consumption and cocaine use. Overweight and obese women should be encouraged toward weight reduction. Future translational studies will better link circadian rhythm disturbances with human fertility.