Luteinizing Hormone β-subunit Gene Polymorphisms and Androgen Levels are Less Predictive of Ovarian Response in Polycystic Ovary Syndrome In vitro Fertilisation Women: A Nested Case-Control Study

Suheimi, Irham and Wiweko, Budi and Thuffi, Rosalina and Muharam, Raden and Asmarinah, Asmarinah and Indriatmi, Wresti and Malik, Safarina G. and Boediono, Arief and Hidayat, Syarief Thaufik and Sini, Ivan and Sirait, Batara I. (2025) Luteinizing Hormone β-subunit Gene Polymorphisms and Androgen Levels are Less Predictive of Ovarian Response in Polycystic Ovary Syndrome In vitro Fertilisation Women: A Nested Case-Control Study. Journal of Human Reproductive Sciences, 18 (4). pp. 239-245.

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Abstract

Abstract Background: Genetic polymorphisms in the luteinizing hormone (LH) β-subunit gene have been associated with responses to controlled ovarian hyperstimulation (COH) in in vitro fertilisation (IVF) patients. Variants in rs1800447 and rs34349826 may increase androgen production, potentially impairing folliculogenesis and ovarian response. Aim: The aim of this study was to investigate the clinical significance of LH β-subunit single-nucleotide polymorphism (SNP) (rs1800447 and rs34349826), levels of testosterone, sex hormone-binding globulin (SHBG) and free testosterone index in predicting COH response in polycystic ovary syndrome (PCOS) women. Settings and design: This nested case-control study enlisted 122 women with PCOS in the Morula IVF Jakarta Clinic, Jakarta, Indonesia. Materials and methods: The selection of cases and controls was in the ratio of 1:2. Blood samples were taken on day 2 or 3 of menstrual cycle. Sanger sequencing was utilised to genotype the LH β-subunit genes (rs1800447 and rs34349826). Levels of testosterone and SHBG were measured to calculate the free testosterone index. Women were retrospectively grouped as hyporesponders (<8 oocytes) or normo/hyperresponders (≥8 oocytes) according to the number of retrieved oocytes. Statistical analysis used: SPSS Software version 21.0 (IBM Corp., USA). Independent t-test or Mann-Whitney test for numerical variables and Chi-square test for categorical variables were employed. Results: A unique automatic transmission (AT) variant in both rs1800447 and rs34349826 LH β-subunit was discovered, which has yet been reported previously. Notably, the proportion of heterozygous LH β genotypes (AT and AG) in both rs1800447 and rs34349826 was similar between hyporesponder and normo/hyperresponder groups (P > 0.05). All participants were normoandrogenic PCOS women, indicated by the normal level of testosterone (0.84 ± 0.35 nmol/L) and SHBG (57.87 ± 29.20 nmol/L) as well as free testosterone index (1.88 ± 1.34). No difference in testosterone levels, SHBG and free testosterone index was observed among the studied groups (P > 0.05). Conclusion: LH β gene SNPs (rs1800447 and rs34349826), testosterone level, SHBG level and free testosterone index were not significantly correlated and less effective clinical indicators for COH response in normoandrogenic PCOS women. Keywords: Androgen; clinical relevance; in vitro fertilisation; luteinizing hormone β-subunit; polycystic ovary syndrome; polymorphisms.

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