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Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of this study was to assess the relation between BMP15 and GDF9 variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of BMP15 and GDF9 were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of BMP15 and GDF9 genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32-4.11, p = 0.004).The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Purpose: One of the most common problems in reproductive medicine is recurrent miscarriage (RM). There is increasing evidence showing genetic susceptibility of women is an important risk factor in the occurrence of RM. In recent years, there is a growing interest in sulfate and its role in fetal development. A novel mechanism of SULF1 has been demonstrated for modifying the activities of some growth factors and signalling molecules that have major roles during embryogenesis. The aim of present study was to evaluate the association of SULF1 gene polymorphism (rs6990375 G > A) in Iranian patients with RM., Methods: We established a case-control study of 200 Iranian women: 100 patients with the history of two or more RM as cases and 100 healthy women with at least two cases of successful pregnancy and no history of miscarriage as controls. The polymorphism was examined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method., Results: The genotypic analysis between case and controls showed significant differences (p-value = 0.000). Allelic analysis showed no significant correlation (Χ2 = 3.36, p-value = 0.066). The heterozygous genetic variant was significantly higher among healthy women (OR = 12.67, 95% CI = 6.47-24.79)., Conclusions: Our data showed that rs6990375 polymorphism of SULF1 gene could be among one of the factors related to RM in Iranian women. Further evaluation of this polymorphism may be important and need further studies.

Purpose: This is a case- control study to determine whether G1733A polymorphism of androgen receptor gene is associated with an increased risk for recurrent spontaneous abortion (RSA)., Method: A total of 85 women with at least two recurrent spontaneous abortion before 20th week of gestation composed the study group. Subjects were genotyped by the polymerase chain reaction restriction fragment length polymorphism method., Results: The observed frequencies of GG, GA and AA genotypes of the G1733A polymorphism were 5.89 %, 82.35 % and 11.76 %, respectively, for the patient group and 71.76 %, 23.51 % and 4.71 %, respectively, for the control group. Allele frequencies of the G1733A polymorphism among patients and controls were 0.47 and 0.84, respectively, for the dominant allele (G) (wild type) and 0.53 and 0.16, respectively, for the A allele (mutant type)., Conclusions: These results indicated that the androgen receptor G1733A polymorphism is strongly associated with increased risk for RSA.