P–569 Woman with CYP19A1 TC/CC genotype have increased susceptibility to infertility development, independently of the cause
Authors: Alves M , Almeida M , Oliani A H , Breitenfeld L , Ramalhinho A 
Published: August 2021

Study question

Is TC/CC genotype of codon 39 at CYP19A1 gene associated with the development of female infertility?

Summary answer

Yes, CYP19A1 codon 39 TC/CC genotype is associated with increased susceptibility to infertility development in women, regardless of associated cause.

What is known already

Aromatase protein is responsible for the aromatization of androgens into estrogens. This protein that catalyzes the final step in biosynthesis of estrogens is encoded by the gene CYP19A1. The CYP19A1 gene is located on chromosome 15q21.1. It is a member of the cytochrome P450 superfamily which are monooxygenases that catalyze many reactions involved in steroidogenesis. TC/CC genotype of codon 39 at CYP19A1 gene results in an increase of aromatase activity and thus affect the hormone levels which can lead to the development of various diseases, including infertility.

Study design, size, duration

A case-control study was designed to investigate the association of CYP19A1 gene polymorphism with female infertility. Case subjects, 201 women with infertility established as women under 39 years of age, that failed to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse. 161 fertile female controls, with no previous history of infertility, no previous history of gynecological pathologies compatible with infertility, and no history of IVF treatments, were selected.

Participants/materials, setting, methods

Blood was collected by venous puncture and genomic DNA was extracted. CYP19A1 genotyping was performed by polymerase chain reaction-based methods with confronting two-pair primers. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression.

Main results and the role of chance

Significant statistical association of the TC/CC genotype combined with endometriosis risk was found, with reference to TT genotype (OR 4.554; 95% CI 2.209–9.386; p &lt; 0.001). We also found an increased risk of developing polycystic ovary syndrome (PCOS) associated with TC/CC genotype (OR 5.317; 95% CI 2.767–10.215; p &lt; 0.001). We also observed an increased prevalence of premature ovarian failure associated with TC/CC genotype (OR 3.376; 95% CI 1.672–6.815; p = 0.001) and verified an increased prevalence of tubal pathology in carriers of TC/CC genotype (OR 3.231; 95% CI 1.653–6.314; p = 0.001). Finally, a strong association of TC/CC genotype with female infertility, regardless of the cause was found (OR 4.232; 95% CI 2.710–6.609; p &lt; 0.001). In conclusion, TC/CC genotype is associated with increased susceptibility to infertility development in women.

Limitations, reasons for caution

The sample size may eventually be considered small, despite the strong significance found.

Wider implications of the findings: There are not many studies in this area and the few existing exhibit disparate results. The association of TC/CC genotype with endometriosis was observed in a few studies, but some disagree. This difference could be attributed to the notable heterogeneity across the different studies.

Trial registration number

Not applicable