Evaluation and treatment of low responders in assisted reproductive technology: a challenge to meet

To investigate the various methods of evaluation and treatment of patients with a low response to controlled ovarian hyperstimulation in assisted reproductive technologies (ART).

Review and analysis of relevant studies published in the last decade, identified through the literature and Medline searches.

While a universally accepted definition for low responders is still lacking, these patients are reported to represent about 10% of the ART population. Several ovarian reserve screening techniques have been proposed; however, currently the best-characterized and most sensitive screening tools available are the basal day 3 serum follicle-stimulating hormone level and the clomiphene citrate challenge test. When abnormal, these tests allow physicians to counsel patients that their prognosis for conception is poor. Although the presence of a normal result does indicate better long-term chances for conception, on age-related decline in fecundity remains and patient age should still be considered when counseling patients with normal screening results. Several stimulation protocols have been applied in the low-response group with varying success. Recent studies show that the use of a minidose gonadotropin-releasing hormone-agonist protocol may result in significantly decreased cycle cancellations as well as increased clinical and ongoing pregnancies, and thus is proposed as a first-line therapy. Studies evaluating supplementary forms of treatment to the ovulation induction regimen show improved outcome when pretreating with oral contraceptives, whereas there seems to be no benefit from cotreatment with growth hormone or glucocorticoids. Blastocyst culture and transfer and assisted hatching in low responders are still under evaluation, whereas natural cycle in vitro fertilization may be used in cases of repeated failures as a last option before resorting to oocyte donation or adoption. Future possible forms of treatment like in vitro maturation of immature human oocytes, cytoplasm, and nuclear transfer currently are experimental in nature and their efficacy has still to be proven.

The evaluation and treatment of low responders in ART remains a challenge. Understanding of the underlying etiology and pathophysiology of this disorder may help the clinician to approach it successfully.