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. 2021 Oct;38(10):2769-2779.
doi: 10.1007/s10815-021-02276-0. Epub 2021 Aug 3.

Variants Ala307Ala and Ser680Ser of 307 and 680 FSHr polymorphisms negatively influence on assisted reproductive techniques outcome and determine high probability of non-pregnancy in Caucasian patients

Belén Monge-Ochoa  1 , Luis Montoro  2 , Elisa Gil-Arribas  3 , Julio Montoya  1   4   5 , Eduardo Ruiz-Pesini  1   4   5 , Manuel J López-Pérez  1 , Francisco de Castro  2 , Carmen Díez-Sánchez  6
Affiliations

Variants Ala307Ala and Ser680Ser of 307 and 680 FSHr polymorphisms negatively influence on assisted reproductive techniques outcome and determine high probability of non-pregnancy in Caucasian patients

Belén Monge-Ochoa et al. J Assist Reprod Genet. 2021 Oct.

Abstract

Purpose: To determine the influence of different genotypes of Ala307Thr and Asn680Ser FSHr polymorphisms on controlled ovarian stimulation (COS) outcome and pregnancy.

Methods: This study collected blood and physiological and clinical parameters of 517 Caucasian patients (Statistical power ≥ 80%) that underwent COS treatment. Genotypes of Ala307Thr and Asn680Ser polymorphisms were determined using PCR amplification followed by Bsu36I and BsrI digestion, respectively.

Results: Ala307Ala and Ser680Ser genotypes associated to worse parameters of COS outcome (preovulatory follicles P = 0.05, in both), justifying their lower pregnancy rate than Non-Ala307Ala, P = 0.01 and Non-Ser680Ser, P = 0.004, respectively or together, (P = 0.003). Within the Non-Ala307Ala group, Thr307Thr genotype showed higher number of fertilized oocytes (P = 0.04) and embryos (P = 0.01) than Non-Thr307Thr, but no influence on pregnancy rate. Ala307Ala and Ser680Ser patients doubled probability of non-pregnancy than Non-Ala307Ala (odds ratio = 2.0) and Non-Ser680Ser (odds ratio = 2.11), respectively. Ala307Ala and Ser680Ser genotypes tend to appear together (P < 0.0001), which increases the probability of non-pregnancy.

Conclusions: Ala307Ala and Ser680Ser genotypes of 307 and 680 FSHr polymorphisms associate to worse COS outcome than its respective Non-Ala307Ala and Non-Ser680Ser. Within the Non-Ala307Ala genotypes, Thr307Thr, although shows higher Fertilized Oocytes and Embryos, do not influence on pregnancy rate. Ala307Ala and Ser680Ser genotypes double the probability of Non-Pregnancy than their respective Non-Ala307Ala and Non-Ser680Ser genotypes. Furthermore, the strong tendency of these genotypes to appear together worsens the probability of pregnancy in these patients.

Keywords: Ala307Thr polymorphism;; Asn680Ser polymorphism; Assisted reproductive techniques;; Controlled ovarian stimulation (COS);; FSHr polymorphisms;.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
TD FSH and Estradiol in Pregnancy (n= 193) and Non-Pregnancy (n= 324) groups. Student’s t-test analysis: TD FSH (IU) [Pregnancy (1.684.5 ± 654.8) vs. Non-Pregnancy (1.832.1 ± 705.1); P = 0.02]; Estradiol (pg/mL) [Pregnancy (1.382.9 ± 789.1) vs. Non-Pregnancy (1.228.1 ± 728.9); P = 0.02]
Fig. 2
Fig. 2
Physiological parameters after COS treatment. Pregnancy (n=193), Non-Pregnancy (n=324). Student’s t-test analysis: Basal FSH (IU/mL) [Pregnancy (7.3 ± 1.99) vs. Non-Pregnancy (7.4 ± 2.31); P >0.05]; Preovulatory follicles (PF) [Pregnancy (10.7 ± 5.6) vs. Non-Pregnancy (9.4 ± 5.6); P = 0.007]; Recruited Oocytes (RO) [Pregnancy (8.7 ± 4.2) vs. Non-Pregnancy (7.9 ± 4.1); P = 0.04], Fertilized Oocytes (FO) [Pregnancy (5.8 ± 3.4) vs. Non-Pregnancy (4.8 ± 3.3); P = 0.0003] and Embryos (E) [Pregnancy (5.4 ± 3.2) vs. Non-Pregnancy (4.3 ± 2.9); P <0.0001]
Fig. 3
Fig. 3
Analysis of inheritance models of 307 and 680 FSHr polymorphisms genotypes for Basal FSH (B FSH), Preovulatory Follicles (PF), Recruited Oocytes (RO), Fertilized Oocytes (FO) and Embryos (E) when Student’s t-test were applied. A: Recessive model in 307 [Ala/Ala (n= 85); Non-Ala/Ala (n= 432)]: statistically significant differences have been found in Basal FSH (IU/mL) [Ala/Ala (7.9 ± 2.3) vs. Non-Ala/Ala (7.3 ± 2.1); P = 0.01] and PF [Ala/Ala (8.8 ± 5.2) vs. Non-Ala/Ala (10.2 ± 5.7); P = 0.05]. However, non-significant differences have been found in RO [Ala/Ala (7.4 ± 3.9) vs. Non-Ala/Ala (8.4 ± 4.29) (P > 0.05)]; FO [Ala/Ala (4.7 ± 3.3) vs. Non-Ala/Ala (5.3 ± 3.4) (P > 0.05)]; nor in E [Ala/Ala (4.2 ± 3.0) vs. Non-Ala/Ala (4.7 ± 3.1) (P > 0.05)]. B: Dominant model in 307 [Thr/Thr (n= 134); Non-Thr/Thr (n= 383)] showed non statistically significant differences in Basal FSH (IU/mL) [Thr/Thr (7.2 ± 2.0) vs. Non-Thr/Thr (7.4 ± 2.2) (P > 0.05)]; PF [Thr/Thr (10.7 ± 5.6) vs. Non-Thr/Thr (9.7 ± 5.6) (P > 0.05)] and RO [Thr/Thr (9.0±4.1) vs. Non-Thr/Thr (9.0±4.2) (P > 0.05)]. However, FO [Thr/Thr (5.7±3.3) vs. Non-Thr/Thr (5.0±3.4) (P = 0.04)] and E [Thr/Thr (5.1±3.0) vs. Non-Thr/Thr (4.5±3.1) (P = 0.01)] showed statistically significant differences. C: Recessive model in 680 [Ser/Ser (n= 60) and Non-Ser/Ser (n= 457)]. Statistically significant differences have also been found in Basal FSH (IU/mL) [Ser/Ser (8.0 ± 2.7) vs. Non-Ser/Ser (7.3 ± 2.1); P = 0.02], PF [Ser/Ser (8.6 ±3.9) vs. Non-Ser/Ser (10.1 ± 5.8), P = 0.05]. Nevertheless, no statistically significant differences have been found in RO [Ser/Ser (7.5 ± 3.5) vs. Non-Ser/Ser (8.3 ± 4.3); P > 0.05]; FO [Ser/Ser (4.6 ± 2.9) vs. Non-Ser/Ser (5.3 ± 3.4); P > 0.05] nor in E [Ser/Ser (4.1 ± 3.1) vs. Non-Ser/Ser (4.7 ± 3.1); P > 0.05]. D: Dominant model in 680 [Asn/Asn (n= 182) and Non-Asn/Asn (n= 335)]. Basal FSH (IU/mL) [Asn/Asn (7.2 ± 1.9) vs. Non-Asn/Asn (7.5 ± 2.3); P > 0.05]; PF [Asn/Asn (10.1 ± 5.6) vs. Non-Asn/Asn (9.8 ± 5.7); P > 0.05]; RO [Asn/Asn (8.7 ± 4.5) vs. Non-Asn/Asn (8.0 ± 4.0); P > 0.05]; FO [Asn/Asn (5.5 ± 3.6) vs. Non-Asn/Asn (5.0 ± 3.3); P > 0.05]; E [Asn/Asn (4.9 ± 3.2) vs. Non-Asn/Asn (4.6 ± 3.0); P > 0.05], without statistically significant differences in all parameters
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References

    1. Wyns C, Bergh C, Calhaz-Jorge C, De Geyter C, Kupka MS, Mocanu E, et al. ART in Europe, 2015: results generated from European registries by ESHRE The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod Open. 2020:1–17. - PMC - PubMed
    1. ESHRE Guideline Group on Ovarian Stimulation. Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, Kolibianakis E, Kunicki M, Marca A, Lainas G, Clef NL, Massin N, Mastenbroek S, Polyzos N, Sunkara SK, Timeva T, Töyli M, Urbancsek J, Vermeulen N, Broekmans F. Erratum: ESHRE guideline: ovarian stimulation for IVF/ICSI. Hum Reprod Open. 2020;2020(4):hoaa067. doi: 10.1093/hropen/hoaa067. - DOI - PMC - PubMed
    1. Kaiser UB. The pathogenesis of the ovarian hyperstimulation syndrome. N Engl J Med. 2003;349:729–732. - PubMed
    1. Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002;8:559–577. - PubMed
    1. Nenonen H, Lindgren I, Prahl A, Trzybulska D, Kharraziha I, Hultén M, et al. The N680S variant in the follicle-stimulating hormone receptor gene identifies hyperresponders to controlled ovarian stimulation. Pharmacogenet Genomics. 2019;29:114–120. - PMC - PubMed