Genetic determination of the ovarian reserve: a literature review

Moiseeva, A. V.; Kudryavtseva, V. A.; Николенко, В.Н.; Gevorgyan, Marine M.; Unanyan, A. L.; Bakhmet, A. A.; Sinelnikov, Mikhail Y.

doi:10.1186/s13048-021-00850-9

Cited by 8 publications

(7 citation statements)

References 63 publications

(63 reference statements)

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“…The ovarian reserve indicators most widely used in clinical practice include AMH levels and AFC. In addition, changes in the levels of FSH, LH, and E2 can support the prognostic evaluation of women with DOR [ 29 , 30 ]. The control group consisted of 35 healthy volunteers with no history of infertility or an ovarian reserve appropriate for reproductive age, as assessed using serum AMH assay and ultrasound evaluation of AFC performed during the early follicular phase ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation

Palese,

Ferretti,

Perruolo

et al. 2024

Life

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Semaphorin 3A (SEMA3A) plays a crucial role in the development, differentiation, and plasticity of specific types of neurons that secrete Gonadotropin-Releasing Hormone (GnRH) and regulates the acquisition and maintenance of reproductive competence in humans and mice. Its insufficient expression has been linked to reproductive disorders in humans, which are characterized by reduced or failed sexual competence. Various mutations, polymorphisms, and alternatively spliced variants of SEMA3A have been associated with infertility. One of the common causes of infertility in women of reproductive age is diminished ovarian reserve (DOR), characterized by a reduced ovarian follicular pool. Despite its clinical significance, there are no universally accepted diagnostic criteria or therapeutic interventions for DOR. In this study, we analyzed the SEMA3A plasma levels in 77 women and investigated their potential role in influencing fertility in patients with DOR. The results revealed that the SEMA3A levels were significantly higher in patients with DOR than in healthy volunteers. Furthermore, the SEMA3A levels were increased in patients who underwent fertility treatment and had positive Beta-Human Chorionic Gonadotropin (βHCG) values (β+) after controlled ovarian stimulation (COS) compared to those who had negative βHCG values (β−). These findings may serve as the basis for future investigations into the diagnosis of infertility and emphasize new possibilities for the SEMA3A-related treatment of sexual hormonal dysfunction that leads to infertility.

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Section: Resultsmentioning

confidence: 99%

Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation

Palese,

Ferretti,

Perruolo

et al. 2024

Life

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“…TB, a global health concern, is known to affect various organ systems, but its effects on fertility have been less well-documented 25,26 . Ovarian reserve function refers to the ability of the growth and development of follicles and oocyte fertilization after ovulation, which is determined by the quantity and quality of the remaining oocytes in the ovaries and reflects a woman's reproductive potential 27 . The most commonly used biomarkers in clinical practice for assessing the ovarian reserve function include age, basal FSH, AFC, and AMH 28 .…”

Section: Discussionmentioning

confidence: 99%

Analysis of the potential regulatory mechanisms of female and latent genital tuberculosis affecting ovarian reserve function using untargeted metabolomics

Wang,

Zhang,

Dai

et al. 2024

Sci Rep

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Female and latent genital tuberculosis (FGTB and LGTB) in young women may lead to infertility by damaging ovarian reserve function, but the regulatory mechanisms remain unclear. In this study, we investigated the effects of FGTB and LGTB on ovarian reserve function and potential regulatory mechanisms by untargeted metabolomics of follicular fluid, aiming to provide insights for the clinical management and treatment approaches for afflicted women. We recruited 19 patients with FGTB, 16 patients with LGTB, and 16 healthy women as a control group. Clinical data analysis revealed that both the FGTB and LGTB groups had significantly lower ovarian reserve marker levels compared to the control group, including lower anti-Müllerian hormone levels (FGTB: 0.82 [0.6, 1.1] μg/L; LGTB: 1.57 [1.3, 1.8] μg/L vs. control: 3.29 [2.9, 3.5] μg/L), reduced antral follicular counts (FGTB: 6 [5.5, 9.5]; LGTB: 10.5 [7, 12.3] vs. control: 17 [14.5, 18]), and fewer retrieved oocytes (FGTB: 3 [2, 5]; LGTB: 8 [4, 8.3] vs. control: 14.5 [11.5, 15.3]). Conversely, these groups exhibited higher ovarian response marker levels, such as longer gonadotropin treatment days (FGTB: 12 [10.5, 12.5]; LGTB: 11 [10.8, 11.3] vs. control: 10 [8.8, 10]) and increased gonadotropin dosage requirements (FGTB: 3300 [3075, 3637.5] U; LGTB: 3037.5 [2700, 3225] U vs. control: 2531.25 [2337.5, 2943.8] U). All comparisons were statistically significant at P < 0.05. The results suggested that FGTB and LGTB have adverse effects on ovarian reserve and response. Untargeted metabolomic analysis identified 92 and 80 differential metabolites in the control vs. FGTB and control vs. LGTB groups, respectively. Pathway enrichment analysis revealed significant alterations in metabolic pathways in the FGTB and LGTB groups compared to the control group (P < 0.05), with specific changes noted in galactose metabolism, biotin metabolism, steroid hormone biosynthesis, and nicotinate and nicotinamide metabolism in the FGTB group, and caffeine metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, and glycerophospholipid metabolism in the LGTB group. The analysis of metabolic levels has revealed the potential mechanisms by which FGTB and LGTB affect ovarian reserve function, namely through alterations in metabolic pathways. The study emphasizes the importance of comprehending the metabolic alterations associated with FGTB and LGTB, which is of considerable relevance for the clinical management and therapeutic approaches in afflicted women.

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“…The understanding of the etiology of DOR is limited, with current evidence suggesting a complex interplay of genetic and environmental factors. Although variants in several genes have been associated with an increased risk for DOR, including FMR1 , FMR2 , AMHR2 , LHCGR , BMP15 , TR53 , GDF9 , FSHR , and NOBOX , the underlying genetic mechanism remains largely unknown [ 9 , 10 ]. And the identification of specific genetic causes for DOR is hindered by the complex inheritance pattern and the lack of large-scale genetic studies.…”

Section: Introductionmentioning

confidence: 99%

Identification of compound heterozygous variants in MSH4 as a novel genetic cause of diminished ovarian reserve

Wan,

Hong,

et al. 2023

Reprod Biol Endocrinol

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Background Diminished ovarian reserve (DOR) is a common cause of female infertility, with genetic factors being a significant contributor. However, due to high genetic heterogeneity, the etiology of DOR in many cases remains unknown. In this study, we analyzed the phenotype of a young woman with primary infertility and performed molecular genetic analysis to identify the genetic cause of her condition, thus providing important insights for genetic counseling and reproductive guidance. Methods We collected the patient’s basic information, clinical data, as well as diagnostic and therapeutic history and performed whole-exome sequencing on her peripheral blood. Candidate pathogenic variants were validated by Sanger sequencing in family members, and the pathogenicity of variants was analyzed using ACMG guidelines. We used bioinformatics tools to predict variant effects on splicing and protein function, and performed in vitro experiments including minigene assay and expression analysis to evaluate their functional effects on HEK293T. Results We identified biallelic MSH4 variants, c.2374 A > G (p.Thr792Ala) and c.2222_2225delAAGA (p.Lys741Argfs*2) in the DOR patient. According to ACMG guidelines, the former was classified as likely pathogenic, while the latter was classified as pathogenic. The patient presented with poor oocyte quantity and quality, resulting in unsuccessful in vitro fertilization cycles. Bioinformatics and in vitro functional analysis showed that the c.2374 A > G variant altered the local conformation of the MutS_V domain without decreasing MSH4 protein expression, while the c.2222_2225delAAGA variant led to a reduction in MSH4 protein expression without impacting splicing. Conclusions In this study, we present evidence of biallelic variants in MSH4 as a potential cause of DOR. Our findings indicate a correlation between MSH4 variants and reduced oocyte quality, as well as abnormal morphology of the first polar body, thereby expanding the phenotypic spectrum associated with MSH4 variants. Furthermore, Our study emphasizes the importance of utilizing whole-exome sequencing and functional analysis in diagnosing genetic causes, as well as providing effective genetic counseling and reproductive guidance for DOR patients.

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Genetic determination of the ovarian reserve: a literature review

Cited by 8 publications

References 63 publications

Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation

Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation

Analysis of the potential regulatory mechanisms of female and latent genital tuberculosis affecting ovarian reserve function using untargeted metabolomics

Identification of compound heterozygous variants in MSH4 as a novel genetic cause of diminished ovarian reserve

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