Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-26T03:22:47.615Z Has data issue: false hasContentIssue false
  • English
  • Français

Do follicle-stimulating hormone receptor polymorphisms in infertile men influence intracytoplasmic sperm injection outcomes? A prospective cohort study

Published online by Cambridge University Press:  22 September 2022

Chadi Fakih ,
Georges Raad Open the ORCID record for Georges Raad [Opens in a new window] ,
Mona Ghamloush ,
Marwa Bazzi ,
Ibrahim Fakih ,
Neemtallah Safi ,
Claira Costantine ,
Youmna Mourad  and
Fadi Fakih
Chadi Fakih*
Affiliation:
Al Hadi Laboratory and Medical Center, Beirut, Lebanon Lebanese University, Faculty of Medicine, Department of Obstetrics and Gynecology, Lebanon
Georges Raad
Affiliation:
Al Hadi Laboratory and Medical Center, Beirut, Lebanon
Mona Ghamloush
Affiliation:
Al Hadi Laboratory and Medical Center, Beirut, Lebanon
Marwa Bazzi
Affiliation:
Al Hadi Laboratory and Medical Center, Beirut, Lebanon
Ibrahim Fakih
Affiliation:
St Joseph University (USJ), Faculty of Sciences, Lebanon
Neemtallah Safi
Affiliation:
Lebanese University, Faculty of Medicine, Department of Obstetrics and Gynecology, Lebanon
Claira Costantine
Affiliation:
Lebanese University, Faculty of Medicine, Department of Obstetrics and Gynecology, Lebanon
Youmna Mourad
Affiliation:
Al Hadi Laboratory and Medical Center, Beirut, Lebanon
Fadi Fakih
Affiliation:
Al Hadi Laboratory and Medical Center, Beirut, Lebanon
*
Author for correspondence: Chadi Fakih. Al Hadi Laboratory and Medical Center, Beirut, Lebanon. Tel: +961 76 755442. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

The follicle-stimulating hormone (FSH) and its receptor regulate the quantity and quality of spermatozoa production. Several studies have analyzed the effect of single nucleotide polymorphisms (SNPs) in exon 10 of the FSH receptor (FSHR) on basic semen parameters without yet reaching a firm consensus. The aim of this study was to evaluate the effect of p.Thr307Ala and p.Asn680Ser polymorphisms in exon 10 of the FSHR gene, in infertile men, on intracytoplasmic sperm injection (ICSI) outcomes. This study was conducted between March 2019 and February 2020 on infertile couples undergoing ICSI at Al Hadi Laboratory and Medical Center, Lebanon. Couples with severe infertility factors that may impair gametogenesis/embryogenesis (e.g. advanced maternal age, premature ovarian failure, underwent gonadotoxic treatments, etc.) were excluded from the study. Semen and blood samples were collected from infertile men on the day of oocyte collection. Infertile men (n = 173) were screened for FSHR variants using polymerase chain reaction-restriction fragment length polymorphism. Moreover, fertilization rates, embryo quality, and pregnancy outcomes were evaluated. Higher sperm concentrations were found in the p.Thr307Ala group than the p.Thr307Thr (P < 0.01) and p.Ala307Ala (P < 0.05) groups. Furthermore, fertilization rate was significantly lower in the p.Ala307Ala genotype than in the p.Thr307Thr genotype (P < 0.05). We showed that FSHR variants in infertile men undergoing ICSI could affect sperm concentration, motility, and fertilization rates. Therefore, it will be important to confirm these results in further studies using a larger sample size.

Keywords

FertilizationFollicle-stimulating hormoneHumanICSIPolymorphismSingle NucleotideZygote
Type
Research Article
Information
Zygote , Volume 30 , Issue 6 , December 2022 , pp. 809 - 818
Copyright
© The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

These authors contributed equally to the study.

References

Aghajanpour, S., Ghaedi, K., Salamian, A., Deemeh, M. R., Tavalaee, M., Moshtaghian, J., Parrington, J. and Nasr-Esfahani, M. H. (2011). Quantitative expression of phospholipase C zeta, as an index to assess fertilization potential of a semen sample. Human Reproduction, 26(11), 2950–2956. doi: 10.1093/humrep/der285 CrossRefGoogle ScholarPubMed
ALPHA Scientists in Reproductive Medicine and ESHRE Special Interest Group Embryology (2011). Istanbul consensus workshop on embryo assessment: Proceedings of an expert meeting. Reproductive Biomedicine Online, 22(6), 632–646. doi: 10.1016/j.rbmo.2011.02.001 CrossRefGoogle Scholar
Alviggi, C., Conforti, A., Caprio, F., Gizzo, S., Noventa, M., Strina, I., Pagano, T., De Rosa, P., Carbone, F., Colacurci, N. and De Placido, G. (2016). In estimated good prognosis patients could unexpected “hyporesponse” to controlled ovarian stimulation be related to genetic polymorphisms of FSH receptor? Reproductive Sciences, 23(8), 1103–1108. doi: 10.1177/1933719116630419 CrossRefGoogle ScholarPubMed
Alviggi, C., Conforti, A., Santi, D., Esteves, S. C., Andersen, C. Y., Humaidan, P., Chiodini, P., De Placido, G. and Simoni, M. (2018). Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation: A systematic review and meta-analysis. Human Reproduction Update, 24(5), 599–614. doi: 10.1093/humupd/dmy019 CrossRefGoogle ScholarPubMed
Avendaño, C. and Oehninger, S. (2011). DNA fragmentation in morphologically normal spermatozoa: How much should we be concerned in the ICSI era? Journal of Andrology, 32(4), 356–363. doi: 10.2164/jandrol.110.012005 CrossRefGoogle ScholarPubMed
Bakos, H. W., Henshaw, R. C., Mitchell, M. and Lane, M. (2011). Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertility and Sterility, 95(5), 1700–1704. doi: 10.1016/j.fertnstert.2010.11.044 CrossRefGoogle ScholarPubMed
Bellver, J., Mifsud, A., Grau, N., Privitera, L. and Meseguer, M. (2013). Similar morphokinetic patterns in embryos derived from obese and normoweight infertile women: A time-lapse study. Human Reproduction, 28(3), 794–800. doi: 10.1093/humrep/des438 CrossRefGoogle ScholarPubMed
Castillo, J., Jodar, M. and Oliva, R. (2018). The contribution of human sperm proteins to the development and epigenome of the preimplantation embryo. Human Reproduction Update, 24(5), 535–555. doi: 10.1093/humupd/dmy017 CrossRefGoogle Scholar
Condorelli, R. A., La Vignera, S., Mongioì, L. M., Alamo, A. and Calogero, A. E. (2018). Diabetes mellitus and infertility: Different pathophysiological effects in Type 1 and Type 2 on sperm function. Frontiers in Endocrinology, 9, 268. doi: 10.3389/fendo.2018.00268 CrossRefGoogle ScholarPubMed
Conforti, A., Vaiarelli, A., Cimadomo, D., Bagnulo, F., Peluso, S., Carbone, L., Francesca Di Rella, F. et al. (2019). Pharmacogenetics of FSH Action in the female. Frontiers in Endocrinology, 10 (JUN), 1–7. doi: 10.3389/fendo.2019.00398 CrossRefGoogle ScholarPubMed
Dias, T. R., Alves, M. G., Silva, B. M. and Oliveira, P. F. (2014). Sperm glucose transport and metabolism in diabetic individuals. Molecular and Cellular Endocrinology, 396(1–2), 37–45. doi: 10.1016/j.mce.2014.08.005 CrossRefGoogle ScholarPubMed
Gardner, D. K. DPhil, Lane, M. DPH, Stevens, J., Schlenker, T. and Schoolcraft, W. B. (2000). Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer. Fertility and Sterility, 73(6), 1155–1158. doi: 10.1016/s0015-0282(00)00518-5 CrossRefGoogle ScholarPubMed
Gharesi-Fard, B., Behrouz, Z., Ghasemi, Z., Shakeri, S., Behdin, S., Aghaei, F. and Malek-Hosseini, Z. (2015). The frequency of follicle stimulating hormone receptor gene polymorphisms in Iranian infertile men with azoospermia. International Journal of Reproductive Biomedicine, 13(11), 673–678.Google ScholarPubMed
Greb, R. R., Behre, H. M. and Simoni, M. (2005). Pharmacogenetics in ovarian stimulation – Current concepts and future options. Reproductive Biomedicine Online, 11(5), 589–600. doi: 10.1016/s1472-6483(10)61167-4 CrossRefGoogle ScholarPubMed
Grigorova, M., Punab, M., Poolamets, O., Sõber, S., Vihljajev, V., Žilaitienė, B., Erenpreiss, J., Matulevičius, V., Tsarev, I. and Laan, M. (2013). Study in 1790 Baltic men: FSHR Asn680Ser polymorphism affects total testes volume. Andrology, 1(2), 293–300. doi: 10.1111/j.2047-2927.2012.00028.x CrossRefGoogle ScholarPubMed
Grigorova, M., Punab, M., Punab, A. M., Poolamets, O., Vihljajev, V., Žilaitiene, B., Erenpreiss, J., Matulevičius, V. and Laan, M. (2014). FSHB −211G/T. PLoS ONE, 9(4), e94244. doi: 10.1371/journal.pone.0094244 CrossRefGoogle ScholarPubMed
Harchegani, A., Rahmani, H., Tahmasbpour, E., Shahriary, A., Tahmasbpour, E. and Shahriary, A. (2019). Hyperviscous semen causes poor sperm quality and male infertility through induction of oxidative stress. Current Urology, 13(1), 1–6. doi: 10.1159/000499302 CrossRefGoogle Scholar
Jiang, X. H., Bukhari, I., Zheng, W., Yin, S., Wang, Z., Cooke, H. J. and Shi, Q. H. (2014). Blood-testis barrier and spermatogenesis: Lessons from genetically modified mice. Asian Journal of Andrology, 16(4), 572–580. doi: 10.4103/1008-682X.125401 Google ScholarPubMed
Kashir, J. (2020). Increasing associations between defects in phospholipase C zeta and conditions of male infertility: Not just ICSI failure? Journal of Assisted Reproduction and Genetics, 37(6), 1273–1293. doi: 10.1007/s10815-020-01748-z CrossRefGoogle ScholarPubMed
Keltz, J., Zapantis, A., Jindal, S. K., Lieman, H. J., Santoro, N. and Polotsky, A. J. (2015). Overweight men: Clinical pregnancy after ART is decreased in IVF but not in ICSI cycles. Journal of Assisted Reproduction and Genetics, no. 2010, 539–544. doi: 10.1007/s10815–010–9439-y Google Scholar
Lindgren, I., Giwercman, A., Axelsson, J. and Lundberg Giwercman, Y. L. (2012). Association between follicle-stimulating hormone receptor polymorphisms and reproductive parameters in young men from the general population. Pharmacogenetics and Genomics, 22(9), 667–672. doi: 10.1097/FPC.0b013e3283566c42 CrossRefGoogle ScholarPubMed
Menkveld, R. (2010). Clinical significance of the low normal sperm morphology value as proposed in the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Asian Journal of Andrology, 12(1), 47–58. doi: 10.1038/aja.2009.14 CrossRefGoogle ScholarPubMed
Meseguer, M., Santiso, R., Garrido, N., García-Herrero, S., Remohí, J. and Fernandez, J. L. (2011). Effect of sperm DNA fragmentation on pregnancy outcome depends on oocyte quality. Fertility and Sterility, 95(1), 124–128. doi: 10.1016/j.fertnstert.2010.05.055 CrossRefGoogle ScholarPubMed
Muratori, M. and Baldi, E. (2018). Effects of FSH on sperm DNA fragmentation: Review of clinical studies and possible mechanisms of Action. Frontiers in Endocrinology, 9, 734. doi: 10.3389/fendo.2018.00734 CrossRefGoogle ScholarPubMed
Nicholls, P. K., Harrison, C. A., Walton, K. L., Mclachlan, R. I., O’Donnell, L. O. and Stanton, P. G. (2011). Hormonal regulation of Sertoli cell micro-RNAs at spermiation. Endocrinology, 152(4), 1670–1683. doi: 10.1210/en.2010-1341 CrossRefGoogle ScholarPubMed
Oliveira, P. F., Alves, M. G., Rato, L., Laurentino, S., Silva, J., Sá, R., Barros, A., Sousa, M., Carvalho, R. A., Cavaco, J. E. and Socorro, S. (2012). Effect of insulin deprivation on metabolism and metabolism-associated gene transcript levels of in vitro cultured human Sertoli cells. Biochimica et Biophysica Acta, 1820(2), 84–89. doi: 10.1016/j.bbagen.2011.11.006 CrossRefGoogle ScholarPubMed
Pregl Breznik, B., Kovačič, B. and Vlaisavljević, V. (2013). Are sperm DNA fragmentation, hyperactivation, and hyaluronan-binding ability predictive for fertilization and embryo development in in vitro fertilization and intracytoplasmic sperm injection? Fertility and Sterility, 99(5), 1233–1241. doi: 10.1016/j.fertnstert.2012.11.048 CrossRefGoogle ScholarPubMed
Raad, G., Hazzouri, M., Bottini, S., Trabucchi, M., Azoury, J. and Grandjean, V. (2017). Paternal obesity: How bad is it for sperm quality and progeny health? Basic and Clinical Andrology, 27(1), 1–12. doi: 10.1186/s12610-017-0064-9 CrossRefGoogle ScholarPubMed
Raad, G., Azouri, J., Rizk, K., Zeidan, N. S., Azouri, J., Grandjean, V. and Hazzouri, M. (2019a). Adverse effects of paternal obesity on the motile spermatozoa quality. PLoS ONE, 14(2), e0211837. doi: 10.1371/journal.pone.0211837 CrossRefGoogle ScholarPubMed
Raad, G., Mansour, J., Ibrahim, R., Azoury, J., Azoury, J., Mourad, Y., Fakih, C. and Azoury, J. (2019b). What are the effects of vitamin C on sperm functional properties during direct swim-up procedure? Zygote, 27(2), 69–77. doi: 10.1017/S0967199419000030 CrossRefGoogle ScholarPubMed
Rato, L., Socorro, S., Cavaco, J. E. B. and Oliveira, P. F. (2010). Tubular fluid secretion in the seminiferous epithelium: Ion transporters and aquaporins in Sertoli cells. Journal of Membrane Biology, 236(2), 215–224. doi: 10.1007/s00232-010-9294-x CrossRefGoogle ScholarPubMed
Rato, L., Alves, M. G., Dias, T. R., Lopes, G., Cavaco, J. E., Socorro, S. and Oliveira, P. F. (2013). High-energy diets may induce a pre-diabetic state altering testicular glycolytic metabolic profile and male reproductive parameters. Andrology, 1(3), 495–504. doi: 10.1111/j.2047-2927.2013.00071.x CrossRefGoogle ScholarPubMed
Rato, L., Alves, M. G., Cavaco, J. E. and Oliveira, P. F. (2014). High-energy diets: A threat for male fertility? Obesity Reviews, 15(12), 996–1007. doi: 10.1111/obr.12226 CrossRefGoogle ScholarPubMed
Sakkas, D. and Alvarez, J. G. (2010). Sperm DNA fragmentation: Mechanisms of origin, impact on reproductive outcome, and analysis. Fertility and Sterility, 93(4), 1027–1036. doi: 10.1016/j.fertnstert.2009.10.046 CrossRefGoogle Scholar
Sarasa, J., Jonás, M., Enciso, M., García, L., Leza, A., Steger, K. and Aizpurua, J. (2020). Comparison of ART outcomes in men with altered MRNA protamine 1/protamine 2 ratio undergoing intracytoplasmic sperm injection with ejaculated and testicular spermatozoa, November 2019: 1–6. doi: 10.4103/aja.aja CrossRefGoogle Scholar
Schmitz, C. R., Bastos de Souza, C. A., Genro, V. K., Matte, U., de Conto, E. and Sabino Cunha-Filho, J. (2015). LH (Trp8Arg/Ile15Thr), LHR (InsLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility. Journal of Assisted Reproduction and Genetics, 32(6), 991–997. doi: 10.1007/s10815–015–0477–3 CrossRefGoogle ScholarPubMed
Schubert, M., Pérez Lanuza, L. P. and Gromoll, J. (2019). Pharmacogenetics of FSH action in the male. Frontiers in Endocrinology, 10, 47. doi: 10.3389/fendo.2019.00047 CrossRefGoogle ScholarPubMed
Shimoda, C., Koh, E., Yamamoto, K., Matsui, F., Sugimoto, K., Sin, H. S., Maeda, Y., Kanaya, J., Yoshida, A. and Namiki, M. (2009). Single nucleotide polymorphism analysis of the follicle-stimulating hormone (FSH) receptor in Japanese with male infertility: Identification of codon combination with heterozygous variations of the two discrete FSH receptor gene. Endocrine Journal, 56(7), 859–865. doi: 10.1507/endocrj.K09E-130 CrossRefGoogle ScholarPubMed
Simon, L., Murphy, K., Shamsi, M. B., Liu, L., Emery, B., Aston, K. I., Hotaling, J. and Carrell, D. T. (2014). Paternal influence of sperm DNA integrity on early embryonic development. Human Reproduction, 29(11), 2402–2412. doi: 10.1093/humrep/deu228 CrossRefGoogle ScholarPubMed
Simoni, M. and Casarini, L. (2014). Mechanisms in endocrinology: Genetics of FSH action: A 2014-and-beyond view. European Journal of Endocrinology, 170(3), R91–R107. doi: 10.1530/EJE-13-0624 CrossRefGoogle Scholar
Simoni, M., Santi, D., Negri, L., Hoffmann, I., Muratori, M., Baldi, E., Cambi, M., Marcou, M., Greither, T., Baraldi, E., Tagliavini, S., Carra, D., Lombardo, F., Gandini, L., Pallotti, F., Krausz, C., Rastrelli, G., Ferlin, A., Menegazzo, M., et al. (2016). Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p.N680S: A pharmacogenetic study. Human Reproduction, 31(9), 1960–1969. doi: 10.1093/humrep/dew167 CrossRefGoogle ScholarPubMed
Stanton, P. G. (2016). Regulation of the blood-testis barrier. Seminars in Cell and Developmental Biology, 59, 166–173. doi: 10.1016/j.semcdb.2016.06.018 CrossRefGoogle ScholarPubMed
Tavalaee, M., Kiani-Esfahani, A. and Nasr-Esfahani, M. H. (2017). Relationship between phospholipase C-zeta, semen parameters, and chromatin status. Systems Biology in Reproductive Medicine, 63(4), 259–268. doi: 10.1080/19396368.2017.1298006 CrossRefGoogle ScholarPubMed
Tsitlakidis, D., Katopodi, T., Goulis, D. G., Papadimas, I. and Kritis, A. (2017). Association of follicle-stimulating hormone receptor single nucleotide polymorphisms with fertility in Greek men. Journal of Endocrinological Investigation, 40(7), 721–726. doi: 10.1007/s40618-017-0637-7 CrossRefGoogle ScholarPubMed
Ulloa-Aguirre, A., Zariñán, T., Jardón-Valadez, E., Gutiérrez-Sagal, R. and Dias, J. A. (2018). Structure-function relationships of the follicle-stimulating hormone receptor. Frontiers in Endocrinology, 9, 707. doi: 10.3389/fendo.2018.00707 CrossRefGoogle ScholarPubMed
World Health Organization (2010). WHO laboratory manual for the examination and processing of human semen, 5th edn. World Health Organization. https://apps.who.int/iris/handle/10665/44261 Google Scholar
Wu, W., Cai, H., Sun, H., Lu, J., Zhao, D., Qin, Y., Han, X., Niu, X., Lu, C., Xia, Y., Wang, S., De Moor, B., Marchal, K. and Wang, X. (2012). Follicle stimulating hormone receptor G-29A, 919A>G, 2039A>G polymorphism and the risk of male infertility: A meta-analysis. Gene, 505(2), 388–392. doi: 10.1016/j.gene.2012.02.023 CrossRefGoogle ScholarPubMed
Wu, X. Q., Xu, S. M., Wang, Y. Q., Li, Q., Wang, Z. Q., Zhang, C. L. and Shen, Y. (2015). FSHR gene THr307Ala and Asn680Ser polymorphisms in infertile men: an association study in North China and meta-analysis. Genetics and Molecular Research, 14(2), 5592–5601. doi: 10.4238/2015.May.25.11 CrossRefGoogle ScholarPubMed
Wu, Q., Zhang, J., Zhu, P., Jiang, W., Liu, S., Ni, M., Zhang, M., Li, W., Zhou, Q., Cui, Y. and Xia, X. (2017). The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: an association study and meta-analysis. BMC Medical Genetics, 18(1), 1–15. doi: 10.1186/s12881-017-0441-4 CrossRefGoogle ScholarPubMed
Wunsch, A., Sonntag, B. and Simoni, M. (2007). Polymorphism of the FSH receptor and ovarian response to FSH. Annales d’Endocrinologie, 68(2–3), 160–166. doi: 10.1016/j.ando.2007.04.006 CrossRefGoogle Scholar
Xue, L. T., Wang, R. X., He, B., Mo, W. Y., Huang, L., Wang, S. K., Mao, X. B., Cheng, J. P., Huang, Y. Y. and Liu, R. Z. (2016). Effect of sperm DNA fragmentation on clinical outcomes for Chinese couples undergoing in vitro fertilization or intracytoplasmic sperm injection. Journal of International Medical Research, 44(6), 1283–1291. doi: 10.1177/0300060516664240 CrossRefGoogle ScholarPubMed
Yamaguchi, K., Ishikawa, T., Mizuta, S., Takeuchi, T., Matsubayashi, H., Kokeguchi, S., Habara, T., Ichioka, K., Ohashi, M., Okamoto, S., Kawamura, T., Kanto, S., Taniguchi, H., Tawara, F., Hara, T., Hibi, H., Masuda, H., Matsuyama, T. and Yoshida, H. (2020). Clinical outcomes of microdissection testicular sperm extraction and intracytoplasmic sperm injection in Japanese men with Y chromosome microdeletions. Reproductive Medicine and Biology, 19(2), 158–163. doi: 10.1002/rmb2.12317 CrossRefGoogle ScholarPubMed
Yan, Y., Gong, Z., Zhang, L., Li, Y., Li, X., Zhu, L. and Sun, L. (2013). Association of follicle-stimulating hormone receptor polymorphisms with ovarian response in Chinese women: A prospective clinical study. PLoS ONE, 8(10), e78138. doi: 10.1371/journal.pone.0078138 CrossRefGoogle ScholarPubMed
Zalata, A. A., Hassan, A. H., Nada, H. A., Bragais, F. M., Agarwal, A. and Mostafa, T. (2008). Follicle-stimulating hormone receptor polymorphism and seminal anti-Müllerian hormone in fertile and infertile men. Andrologia, 40(6), 392–397. doi: 10.1111/j.1439-0272.2008.00877.x CrossRefGoogle ScholarPubMed
Zegers-Hochschild, F., Adamson, G. D., de Mouzon, J., Ishihara, O., Mansour, R., Nygren, K., Sullivan, E., Vanderpoel, S., International Committee for Monitoring Assisted Reproductive Technology and World Health Organization. (2009). International committee for monitoring assisted reproductive technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertility and Sterility, 92(5), 1520–1524. doi: 10.1016/j.fertnstert.2009.09.009 CrossRefGoogle ScholarPubMed
Supplementary material: File

Fakih et al. supplementary material

Tables S1-S2

Download Fakih et al. supplementary material(File)
File 17.4 KB