P–584 Female parental consanguinity is associated with a reduced ovarian reserve: a large observational study including 2198 women from the Arabian Peninsula

Study question Is parental consanguinity associated with reduced ovarian reserve in women from the Arabian Peninsula? Summary answer: Women descending from consanguineous unions have a reduced ovarian reserve compared with daughters of non-consanguine couples. What is known already Consanguineous marriage is defined as marriage between second-degree cousins or closer, with high prevalence in the Arabian Peninsula societies. An increased incidence of autosomal recessive diseases has been described in consanguineous marriages compared with non-consanguineous marriages. Despite the known adverse genetic impact of consanguinity, most available studies focus on the fertility of the consanguine couple. Only few publications, including low number of women, evaluated the impact of consanguinity on the fertility of their offspring, suggesting that daughters of consanguine parents might have reduced fertility associated to reduced ovarian reserve. Study design, size, duration A retrospective large-scale observational study was performed including 2482 women from the Arabian Peninsula who had their serum AMH and AFC measured as part of their fertility assessment at ART Fertility Clinics (UAE and Oman), from May 2015 to November 2019. Participants/materials, setting, methods 2482 women from the Arabian Peninsula, aged 19–50 years, were assessed. Consanguinity was defined as women whose parents were first-degree or second-degree cousins. Ovarian reserve was evaluated by Antral Follicle Count (AFC) with transvaginal ultrasound and serum AMH, measured by Elecsys (Cobas, Roche®) for all participants. Women with adnexal surgery history or/and hormonal treatment within previous three months (n = 284) were excluded. Ethical approval was obtained from the Research Ethics Committee (REFA040). Main results and the role of chance After excluding women with previous adnexal surgeries, 2198 women were included for analysis. A total of 605 participants (27.53%) were descendants from consanguineous unions and 1593 (72.47%) reported non-consanguineous kinship of their parents. AMH and AFC (mean±SD) for the consanguineous group were 2.62±2.88 ng/mL and 12.78±9.73 antral follicles, respectively; and AMH and AFC (mean±SD) for the non-consanguineous group were 2.65±2.91 ng/mL and 13.07±9.39 antral follicles, respectively. Women from the consanguinity group were significantly younger (mean±SD: 33.74±6.64 years old) compared with the non-consanguinity group (mean±SD: 34.78±6.64 years old, p < 0.0001). Both groups were similar in BMI (mean±SD: 28.63±5.46 versus 28.41±5.60 kg/m2, p=ns), years of infertility (mean±SD: 3.80±3.68 vs 4.04±3.79, p=ns), type of infertility (primary/secondary), dress code (Hijab/Niqab) and smoking status. As expected, AMH and AFC exhibit an age-dependent decline. To evaluate the differences on ovarian reserve between both groups, a multivariate analysis was performed including age, consanguinity and AMH/AFC. Women from the consanguine group showed significantly lower levels of serum AMH (R2=0.264, p = 0.036) and AFC (R2=0.286, p = 0.003) compared with non-consanguineous women, and the highest differences were found for women below 35 years of age (AMH p = 0.035; AFC p = 0.001). Limitations, reasons for caution Despite the large number of women included, the retrospective study design is a limitation. Results have to be treated with caution before translating into other populations, as these data are obtained from women native to the Arabian Peninsula, with high sociocultural/religious/ethnical similarities, which might differ to other consanguine populations. Wider implications of the findings: Female parental consanguinity is associated with reduced ovarian reserve in the studied population, that might contribute to infertility. Future studies should examine the genetic and epigenetic basis of the current findings. Comprehensive clinical evaluation should include extensive family history and subsequent counselling of the affected couples. Trial registration number Not applicable