| Grant number: | 16/25953-9 |
| Support Opportunities: | Regular Research Grants |
| Start date: | May 01, 2017 |
| End date: | October 31, 2019 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Bianca Alves Vieira Bianco |
| Grantee: | Bianca Alves Vieira Bianco |
| Host Institution: | Centro Universitário Saúde ABC. Santo André , SP, Brazil |
| City of the host institution: | Santo André |
| Associated researchers: | Caio Parente Barbosa ; Denise Maria Christofolini ; Fernando Luiz Affonso Fonseca |
Abstract
Among the main causes of infertility is endometriosis, a chronic inflammatory disease that represents one of the most common benign gynecological disease. It is estimated that 25% to 50% of women with endometriosis are infertile and that 25% to 30% of infertile women have endometrial lesions as the only identifiable cause for infertility. The association between endometriosis and infertility is well established, but the mechanisms responsible for these effects are unknown.Lemos et al (2008) evaluated the ovarian reserve and follicular cohort in infertile women with minimal and mild endometriosis (mean of 29.5 years old) in relation to women with tubal obstruction (mean of 30.5 years old) by mean serum FSH, AMH and transvaginal ultrasonographic evaluation showed that the mean value of FSH did not vary between groups; however, infertile women with endometriosis had significantly lower serum AMH values than the control group. Analysis of the follicular cohort showed that follicle numbers were similar between groups, but the diameter was lower in infertile patients with minimal and mild endometriosis.Corroborating these findings, a study of our group with 340 infertile women with and without endometriosis [126 with infertility by male factor (control group) and 214 with endometriosis (37.9% with minimal/mild endometriosis and 62.1% with moderate/severe endometriosis] revealed that the median serum FSH in the control group was 6.0 IU (5.09 to 7.28 IU), while in the case group it was 6.9 IU (5.4 to 8.75 IU), with a statistically significant difference Significant, p= 0.0016, also suggesting a decrease in ovarian reserve in women with endometriosis.Management of infertility in endometriosis, especially in moderate/severe cases or stages III and IV, is still controversial. A multidisciplinary approach is essential to consider the various treatment options and to provide patients with optimal and individualized care according to different parameters (age, degree of damage and location of lesions, presence or absence of ovarian failure or other factors associated with subfertility, male infertility factor in the couple, etc).In assisted human reproduction, the response to controlled ovarian hyperstimulation is variable and difficult to predict and may result either in satisfactory response or in inadequate response requiring adjustment of FSH dose or ovarian hyperstimulation syndrome, a complication of IVF. The identification of patients with potential to develop hyper or inadequate response to standard treatment would be of great clinical assistance.There are groups of genes that are candidates to affect fertility and, consequently, the response to ovarian hyperstimulation and assisted reproduction outcomes: i) Genes that affect follicular function by exerting a hormonal effect - FSH, FSHR, AMH, AMHR2, ER± , ER², CYP17, CYP19, COMT, MTHFR; And ii) Genes that affect the rate of initial recruitment of the primordial follicular pool to the pool of growing follicles - BMP15, GDF9 and FOXL2. Since these genes are expressed during oogenesis, their mutations can lead to varying degrees of blockage in the formation of germ cells. Small variations in these genes could determine the variability of the follicular pool and thus respond by the variability of response to ovarian hyperstimulation in assisted reproduction treatments.Thus, the aim of the present study is to improve the understanding of mutations and/or polymorphisms in candidate genes that may be important for the advancement of diagnosis and treatment of infertility in women with and without endometriosis through next generation sequencing, correlating these findings with serum levels of FSH, LH, estradiol, AMH and Kisspeptina and results of controlled ovarian hyper stimulation in assisted reproduction treatments. (AU)
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