The continuum of high ovarian response: a rational approach to the management of high responder patient subgroups

Abstract

Ovarian follicular responsiveness to controlled ovarian hyperstimulation (COH) with gonadotropins is extremely variable between individual patients, and even from cycle to cycle for the same patient. High responder patients are characterized by an exaggerated response to gonadotropin administration, accompanied by a higher risk for ovarian hyperstimulation syndrome (OHSS). In spite of its importance, the literature regarding high responders is characterized by heterogeneous classification methodologies. A clear separation should be drawn between risk factors for a high ovarian response and the actual response exhibited by a patient to stimulation. Similarly, it is important to distinguish between high ovarian response and development of clinically significant OHSS. In this article we: (1) review recent publications pertaining to the identification and clinical management of high responders, (2) propose an integrated clinical model to differentiate sub-groups within this population based on this review, and (3) suggest specific protocols for each sub-group. The model is based on a chronological patient assessment in an effort to target treatment based on the specific clinical circumstances. It is our hope that the algorithm we have developed will assist clinicians to supply targeted and precise treatments in order to achieve a favorable reproductive outcome with minimum complications for each patient.

Significant correlation between anti-müllerian hormone and embryo euploidy in a subpopulation of infertile patients

“…Therefore, it is not surprising that ovum euploidy is crucial to achieving and maintaining viable pregnancy. While the association between female age with both AMH (Van Rooij et al, 2002) and egg quality (Hourvitz et al, 2009) is well known, and although AMH reliability as ovarian reserve biomarker has been confirmed (Gat et al, 2015), the specific and direct association between AMH and egg quality is in doubt. To the best of our knowledge, this is the first reported correlation between AMH and blastocyst euploidy rate specifically among patients younger than 37 years old undergoing IVF-PGS.…”

“…Controlled ovarian hyperstimulation protocols for IVF included a standard long agonist-based protocol and a standard antagonist-based protocol. In most cases, the GnRH antagonist protocol was the first line of treatment due to its advantages of reducing the risk of OHSS among high responders (Gat et al, 2015), comparable efficacy and favourable patient tolerance (The European Middle East Orgalutran Study Group, 2001). The exact dosing regimen was determined according to pre-stimulation assessment parameters including age, AMH, antral follicle count (AFC), day 3 FSH, BMI, response to previous stimulation, infertility diagnosis (i.e.…”

Optimal individualization of patient‐oriented ovarian stimulation in Japanese assisted reproductive technology clinics, a review for unique setting with advanced‐age patients

“…Conversely, high responders with a high risk of developing OHSS are defined based on ovarian biomarkers with an AFC >15-20 follicles and/or AMH levels >3-6 ng/mL, based on a systematic review. 35 Furthermore, polycystic ovary syndrome (PCOS) is a main factor associated with a high response to ovarian stimulation. Polycystic ovarian morphology with a high AFC is one of the conditions for the diagnosis of PCOS.…”

Decision points for individualized hormonal stimulation with recombinant gonadotropins for treatment of women with infertility

“…High responders -These patients are characterized by an excessive response to gonadotropin therapy and an increased risk for OHSS [24]. There is no agreed definition for high responders or expected high responder patients [24].…”

“…We propose that high responders are patients from whom you would expect to retrieve !20 oocytes after COS [25]. A large pool of pre-antral follicles has been identified as a risk factor for high response and hyperstimulation, and both high AFC and AMH have been shown to be good predictors of high response [24,[26][27][28][29][30][31]. Proposed biomarkers for identifying high responders are, therefore, a previous high response (!20 oocytes were retrieved after COS), AMH >3.5 ng/mL or AFC !20 [23,24].…”