Abstract
BackgroundA Delphi consensus was conducted to evaluate the influence of single nucleotide polymorphisms (SNPs) in genes encoding gonadotropin and gonadotropin receptors on clinical ovarian stimulation outcomes following assisted reproductive technology (ART) treatment.MethodsNine experts plus two Scientific Coordinators discussed and amended statements plus supporting references proposed by the Scientific Coordinators. The statements were distributed via an online survey to 36 experts, who voted on their level of agreement or disagreement with each statement. Consensus was reached if the proportion of participants agreeing or disagreeing with a statement was >66%.ResultsEleven statements were developed, of which two statements were merged. Overall, eight statements achieved consensus and two statements did not achieve consensus. The statements reaching consensus are summarized here. (1) SNP in the follicle stimulating hormone receptor (FSHR), rs6166 (c.2039A>G, p.Asn680Ser) (N=5 statements): Ser/Ser carriers have higher basal FSH levels than Asn/Asn carriers. Ser/Ser carriers require higher amounts of gonadotropin during ovarian stimulation than Asn/Asn carriers. Ser/Ser carriers produce fewer oocytes during ovarian stimulation than Asn/Asn or Asn/Ser carriers. There is mixed evidence supporting an association between this variant and ovarian hyperstimulation syndrome. (2) SNP of FSHR, rs6165 (c.919G>A, p.Thr307Ala) (N=1 statement): Few studies suggest Thr/Thr carriers require a shorter duration of gonadotropin stimulation than Thr/Ala or Ala/Ala carriers. (3) SNP of FSHR, rs1394205 (−29G>A) (N=1 statement): Limited data in specific ethnic groups suggest that A/A allele carriers may require higher amounts of gonadotropin during ovarian stimulation and produce fewer oocytes than G/G carriers. (4) SNP of FSH β-chain (FSHB), rs10835638 (−211G>T) (N=1 statement): There is contradictory evidence supporting an association between this variant and basal FSH levels or oocyte number. (5) SNPs of luteinizing hormone β-chain (LHB) and LH/choriogonadotropin receptor (LHCGR) genes (N=1 statement): these may influence ovarian stimulation outcomes and could represent potential future targets for pharmacogenomic research in ART, although data are still very limited.ConclusionsThis Delphi consensus provides clinical perspectives from a diverse international group of experts. The consensus supports a link between some variants in gonadotropin/gonadotropin receptor genes and ovarian stimulation outcomes; however, further research is needed to clarify these findings.
Highlights
Infertility is a significant global health problem and socioeconomic burden, affecting 15% of childbearing-age individuals worldwide and with an increasing prevalence over the last two decades [1]
The consensus supports a link between some variants in gonadotropin/gonadotropin receptor genes and ovarian stimulation outcomes; further research is needed to clarify these findings
A total of 18 statements with supporting references were proposed by the Scientific Coordinators
Summary
Infertility is a significant global health problem and socioeconomic burden, affecting 15% of childbearing-age individuals worldwide and with an increasing prevalence over the last two decades [1]. According to the International Committee for Monitoring Assisted Reproductive Technology (ICMART), the global in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) combined delivery rates per fresh aspiration and frozen embryo transfer cycles in 2013 were 24.2% and 22.8%, respectively, with a cumulative delivery rate per aspiration of 30.4% [6]. Delivery rate is closely associated with the number of oocytes retrieved during ovarian stimulation [7] This relationship is even more evident considering how frozen cycles contribute to cumulative live birth rate [8]. In this sense, the goal is to safely retrieve the highest number of mature oocytes in order to get the highest percentage of delivery rate per initiated ovarian stimulation cycle for ART treatment. A Delphi consensus was conducted to evaluate the influence of single nucleotide polymorphisms (SNPs) in genes encoding gonadotropin and gonadotropin receptors on clinical ovarian stimulation outcomes following assisted reproductive technology (ART) treatment
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