Evaluation and Treatment of Low Responders in Assisted Reproductive Technology: A Challenge to Meet

Purpose: To investigate the various methods of evaluationand treatment of patients with a low response to controlledovarian hyperstimulation in assisted reproductive technologies (ART). Methods: Review and analysis of relevant studies publishedin the last decade, identified through the literature and Medlinesearches. Results: While a universally accepted definition for lowresponders is still lacking, these patients are reported torepresent about 10% of the ART population. Several ovarianreserve screening techniques have been proposed; however,currently the best-characterized and most sensitive screeningtools available are the basal day 3 serum follicle-stimulatinghormone level and the clomiphene citrate challenge test.When abnormal, these tests allow physicians to counselpatients that their prognosis for conception is poor. Althoughthe presence of a normal result does indicate better long-termchances for conception, an age-related decline in fecundityremains and patient age should still be considered whencounseling patients with normal screening results. Severalstimulation protocols have been applied in the low-responsegroup with varying success. Recent studies show that theuse of a minidose gonadotropin-releasing hormone-agonistprotocol may result in significantly decreased cycle cancellationsas well as increased clinical and ongoing pregnancies,and thus is proposed as a first-line therapy. Studies evaluatingsupplementary forms of treatment to the ovulation inductionregimen show improved outcome when pretreating withoral contraceptives, whereas there seems to be no benefitfrom cotreatment with growth hormone or glucocorticoids.Blastocyst culture and transfer and assisted hatching in lowresponders are still under evaluation, whereas natural cyclein vitro fertilization may be used in cases of repeated failuresas a last option before resorting to oocyte donation or adoption.Future possible forms of treatment like in vitro maturationof immature human oocytes, cytoplasm, and nucleartransfer currently are experimental in nature and their efficacyhas still to be proven.Conclusions: The evaluation and treatment of low respondersin ART remains a challenge. Understanding of the underlyingetiology and pathophysiology of this disorder may helpthe clinician to approach it successfully.