Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols

Carlo Alviggi, Peter Humaidan, Diego Ezcurra, Carlo Alviggi, Peter Humaidan, Diego Ezcurra

Abstract

Variability in the subfertile patient population excludes the possibility of a single approach to controlled ovarian stimulation (COS) covering all the requirements of a patient. Modern technology has led to the development of new drugs, treatment options and quantitative methods that can identify single patient characteristics. These could potentially be used to match patients with the right treatment options to optimise efficacy, safety and tolerability during COS. Currently, age and follicle-stimulating hormone (FSH) level remain the most commonly used single patient characteristics in clinical practice. These variables only provide a basic prognosis for success and indications for standard COS treatment based on gross patient categorisation. In contrast, the anti-Müllerian hormone level appears to be an accurate predictor of ovarian reserve and response to COS, and could be used successfully to guide COS. The antral follicle count is a functional biomarker that could be useful in determining the dose of FSH necessary during stimulation and the success of treatment. Finally, in the future, genetic screening may allow an individual patient's response to stimulation during COS to be predicted based on genotype. Unfortunately, despite the predictive power of these measures, no single biomarker can stand alone as a guide to determine the best treatment option. In the future, hormonal, functional and genetic biomarkers will be used together to personalise COS.

Figures

Figure 1
Figure 1
Treatment strategies and predicted response to COS based on patient circulating AMH levels. Treatment strategies (right column) and predicted response to COS (middle column) based on patient circulating AMH levels (left column). AMH = anti-Müllerian hormone; COS = controlled ovarian stimulation; GnRH = gonadotrophin releasing hormone; CPR = clinical pregnancy rate; OHSS = ovarian hyperstimulation syndrome; FSH = follicle-stimulating hormone.
Figure 2
Figure 2
Treatment strategies and predicted response to COS based on patient circulating AMH levels. Pregnancy outcomes after COS with r-FSH doses determined by basal FSH, BMI, age and AFC using the CONSORT dose calculator algorithm. AFC = antral follicle count; FSH = follicle-stimulating hormone; ASN = asparagine; Ser680 = serine680; BMI = body mass index; CONSORT = Consolidated Standards of Reporting Trials; COS = controlled ovarian stimulation; r-FSH = recombinant follicle-stimulating hormone. Adapted from Olivennes et al. 2009 [14].
Figure 3
Figure 3
Association between v-LH and FSH consumption. FSH = follicle-stimulating hormone; v-LH = variant luteinising hormone. Adapted from Alviggi et al. 2009 [34].
Figure 4
Figure 4
Basal FSH levels and ampoules of FSH used in COS for patients with variants of the FSH receptor. Basal FSH levels (left panel) and ampoules of FSH used in COS (right panel) for homozygote wild-type (Asn/Asn), heterozygote (Asn/Ser680) and homozygote (Ser680/Ser680) carriers of the Ser680 variant of the FSH receptor. ASN = asparagine; CPRs = clinical pregnancy rates; COS = controlled ovarian stimulation; FSH = follicle-stimulating hormone; r-FSH = recombinant follicle-stimulating hormone; Ser680 = Serine680. Adapted from Perez Mayorga et al. 2000 [37].

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