Blood serum and follicular fluid relaxin: a pilot study of the hormone effects on ovarian function and fertilization efficiency

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract


Hypothesis/aims of study. To date, one of the most important avenues of research in the field of reproductive medicine is the searching for new biochemical markers of oocyte quality and the prediction of the effectiveness of in vitro fertilization (IVF) protocols. The aim of this study was to assess the effect of relaxin levels in blood serum and follicular fluid on the efficiency of ovulation stimulation, fertilization, and characteristics of the embryos.

Study design, materials and methods. This prospective randomized cohort study included 11 patients undergoing infertility treatment in a superovulation stimulation protocol using gonadotropin-releasing hormone antagonists. Age, body mass index, hormonal status, ovarian response, endometrial thickness and structure, the number and quality of oocytes and embryos, as well as fertilization efficiency were assessed. The level of relaxin in blood serum and follicular fluid samples was determined on the day of transvaginal follicle puncture using enzyme immunoassay.

Results. A correlation between follicular fluid relaxin levels and body mass index, age, the number of oocytes, and their fertilization efficiency (p < 0.05) was established. Changes in follicular fluid relaxin level were revealed depending on the gonadotropin preparations (p < 0.05) and triggers of final maturation of oocytes (p < 0.05). The tendency of the effect of gonadotropin doses on circulating relaxin levels, and of the hormone itself on endometrial thickness and the quality of oocytes was determined.

Conclusion. Determination of the relaxin concentration can be considered as a promising method for predicting the result of ovarian stimulation and the efficiency of fertilization in IVF protocols.


Full Text

Restricted Access

About the authors

Olesya N. Bespalova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN-code: 4732-8089

Russian Federation, Saint Petersburg

MD, PhD, DSci (Medicine), Deputy Director 

Valeriya A. Zagaynova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Author for correspondence.
Email: zagaynovav.al.52@mail.ru
ORCID iD: 0000-0001-6971-7024
SPIN-code: 7409-4944

Russian Federation, Saint Petersburg

MD, Post-Graduate Student. The Assisted Reproduction Technology Department

Olga V. Kosyakova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: for.olga.kosyakova@gmail.com
ORCID iD: 0000-0003-4116-0222

Russian Federation, Saint Petersburg

MD, Post-Graduate Student. The Department of Pathology of Pregnancy N 1

Alexander M. Gzgzyan

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; Saint Petersburg State University

Email: ovrt@ott.ru
ORCID iD: 0000-0003-3917-9493

Russian Federation, Saint Petersburg

MD, PhD, DSci (Medicine), Head of the Department of Reproductology, Head of the Assisted Reproduction Technology Department; Professor. The Department of Obstetrics, Gynecology, and Reproductive Sciences, the Faculty of Medicine

Igor Yu. Kogan

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; Saint Petersburg State University

Email: ovrt@ott.ru
ORCID iD: 0000-0002-7351-6900

Russian Federation, Saint Petersburg

MD, PhD, DSci (Medicine), Professor, Corresponding Member of RAS, Director; Professor. The Department of Obstetrics, Gynecology, and Reproductive Sciences, the Faculty of Medicine

Yulia P. Milyutina

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: milyutina1010@mail.ru
ORCID iD: 0000-0003-1951-8312

Russian Federation, Saint Petersburg

PhD, Chairman of the Council of Young Scientists

Natalia N. Tkachenko

the «Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott"

Email: iagmail@ott.ru
ORCID iD: 0000-0001-6189-3488

Russian Federation, Saint Petersburg

PhD, Head of the Laboratory of Endocrinology

Valentina L. Borodina

The «Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott»

Email: iagmail@ott.ru

Russian Federation, Saint Petersburg State University

Laboratory Assistant. The Laboratory of Endocrinology

Elena A. Lesik

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: ovrt@ott.ru
ORCID iD: 0000-0003-1611-6318

Russian Federation, Saint Petersburg

PhD, Senior Researcher. The Laboratory of Early Embryogenesis; Embryologist. The Assisted Reproduction Technology Department

Irina D. Mekina

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: ovrt@ott.ru
ORCID iD: 0000-0002-0813-5845

Russian Federation, Saint Petersburg

PhD, Senior Researcher. The Laboratory of Early Embryogenesis; Senior Embryologist. The Assisted Reproduction Technology Department

Evgenia M. Komarova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: ovrt@ott.ru
ORCID iD: 0000-0002-9988-9879

Russian Federation, Saint Petersburg

PhD, Head of the Laboratory of Early Embryogenesis, Embryologist. The Assisted Reproduction Technology Department

References

  1. Arroyo A, Kim B, Yeh J. Luteinizing hormone action in human oocyte maturation and quality: Signaling pathways, regulation, and clinical impact. Reprod Sci. 2020;27(6):1223-1252. https://doi.org/10.1007/s43032-019-00137-x.
  2. Tong J, Sheng S, Sun Y, et al. Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve. Reproduction. 2017;153(4):443-451. https://doi.org/10.1530/REP-16-0641.
  3. Sun Z, Wu H, Lian F, et al. Human follicular fluid metabolomics study of follicular development and oocyte quality. Chromatographia. 2017;80(6):901-909. https://doi.org/10.1007/s10337-017-3290-6.
  4. Hussein MH, Al-Khafaji QA, Mufedah AJ, et al. Evaluation of lipids in serum and follicular fluid on oocyte and human embryo quality after ICSI. Iraqi Journal of Embryo and Infertility Researches. 2017;7(1):52-61. https://doi.org/10.28969/ijeir.v7.r7.
  5. Poulsen LC, Pla I, Sanchez A, et al. Progressive changes in human follicular fluid composition over the course of ovulation: Quantitative proteomic analyses. Mol Cell Endocrinol. 2019;495:110522. https://doi.org/10.1016/j.mce. 2019.110522.
  6. Niu Z, Ye Y, Xia L, et al. Follicular fluid cytokine composition and oocyte quality of polycystic ovary syndrome patients with metabolic syndrome undergoing in vitro fertilization. Cytokine. 2017;91:180-186. https://doi.org/10.1016/j.cyto. 2016.12.020.
  7. Косякова О.В., Беспалова О.Н. Прогностические возможности релаксина как маркера преждевременных родов // Журнал акушерства и женских болезней. − 2018. − Т. 67. − № 2. − С. 16–25. [Kosyakova OV, Bespalova ОN. Prognostic possibilities of relaxin as a marker of preterm birth. Journal of obstetrics and women’s diseases. 2018;67(2):16-25. (In Russ.)]. https://doi.org/10.17816/JOWD67216-25.
  8. Anand-Ivell R, Ivell R. Regulation of the reproductive cycle and early pregnancy by relaxin family peptides. Mol Cell Endocrinol. 2014;382(1):472-479. https://doi.org/10.1016/ j.mce.2013.08.010.
  9. Marshall SA, Senadheera SN, Parry LJ, Girling JE. The role of relaxin in normal and abnormal uterine function during the menstrual cycle and early pregnancy. Reprod Sci. 2017;24(3): 342-354. https://doi.org/10.1177/1933719116657189.
  10. Bathgate RA, Halls ML, van der Westhuizen ET, et al. Relaxin family peptides and their receptors. Physiol Rev. 2013;93(1):405-480. https://doi.org/10.1152/physrev.00001. 2012.
  11. Luu VV, Hanatate K, Tanihara F, et al. The effect of relaxin supplementation of in vitro maturation medium on the development of cat oocytes obtained from ovaries stored at 4ºC. Reprod Biol. 2013;13(2):122-126. https://doi.org/10.1016/j.repbio.2013.04.002.
  12. Feugang JM, Greene JM, Willard ST, Ryan PL. In vitro effects of relaxin on gene expression in porcine cumulus-oocyte complexes and developing embryos. Reprod Biol Endocrinol. 2011;9:15. https://doi.org/10.1186/1477-7827-9-15.
  13. Vandevoort CA, Mtango NR, Latham KE, Stewart DR. Primate preimplantation embryo is a target for relaxin during early pregnancy. Fertil Steril. 2011;96(1):203-207. https://doi.org/10.1016/j.fertnstert.2011.05.016.
  14. Shirota K, Tateishi K, Koji T, et al. Early human preantral follicles have relaxin and relaxin receptor (LGR7), and relaxin promotes their development. J Clin Endocrinol Metab. 2005;90(1):516-521. https://doi.org/10.1210/jc.2004-0130.
  15. Von Versen-Höynck F, Strauch NK, Liu J, et al. Effect of mode of conception on maternal serum relaxin, creatinine, and sodium concentrations in an infertile population. Reprod Sci. 2019;26(3):412-419. https://doi.org/ 10.1177/1933719118776792.
  16. Patent US-6660531-B2. Stewart DR. Relaxin levels corrlelated to IVF/ET pregnancy success. Available from: https://pubchem.ncbi.nlm.nih.gov/patent/US6660531.
  17. Valkovic AL, Bathgate RA, Samuel CS, Kocan M. Understanding relaxin signalling at the cellular level. Mol Cell Endocrinol. 2019;487:24-33. https://doi.org/10.1016/j.mce. 2018.12.017.
  18. Ryan PL, Klonisch T, Yamashiro S, et al. Expression and localization of relaxin in the ovary of the mare. J Reprod Fertil. 1997;110(2):329-338. https://doi.org/10.1530/jrf.0. 1100329.
  19. Ohleth KM, Zhang Q, Bagnell CA. Relaxin protein and gene expression in ovarian follicles of immature pigs. J Mol Endocrinol. 1998;21(2):179-187. https://doi.org/10.1677/jme.0.0210179.
  20. Fornaro F, Campitiello MR, Pacilio C, Panariello A. Expression of endometrial and folliculum relaxin and reproductive outcome in women undergoing IVF. Giornale Italiano di Ostetricia e Ginecologia. 2010;32(2):81-86.
  21. Bastu E, Gokulu SG, Dural O, et al. The association between follicular fluid levels of cathepsin B, relaxin or AMH with clinical pregnancy rates in infertile patients. Eur J Obstet Gynecol Reprod Biol. 2015;187:30-34. https://doi.org/10.1016/ j.ejogrb.2015.02.009.
  22. Крстич Е.В., Крстич М., Юдаев В.Н. Влияние качества ооцитов и состояния овариального резерва на терапевтический потенциал экстракорпорального оплодотворения у пациенток позднего репродуктивного возраста // Альманах клинической медицины. − 2014. − № 31. − С. 70–75. [Krstic EV, Krstic M, Yudaev VN. Effect of oocytes quality and ovarian reserve on the therapeutic potential of in vitro fertilization in patients of late reproductive age. Almanac of clinical medicine. 2014;(31):70-75. (In Russ.)]. https://doi.org/10.18786/2072-0505-2014-31-70-75.
  23. Comstock IA, Kim S, Behr B, Lathi RB. Increased body mass index negatively impacts blastocyst formation rate in normal responders undergoing in vitro fertilization. J Assist Reprod Genet. 2015;32(9):1299-1304. https://doi.org/ 10.1007/s10815-015-0515-1.
  24. Valckx SD, de Pauw I, de Neubourg D, et al. BMI-related metabolic composition of the follicular fluid of women undergoing assisted reproductive treatment and the consequences for oocyte and embryo quality. Hum Reprod. 2012;27(12):3531-3539. https://doi.org/10.1093/humrep/des350.
  25. Bond CP, Parry LJ, Samuel CS, et al. Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle. Ann N Y Acad Sci. 2005;1041:136-143. https://doi.org/10.1196/annals.1282.020.
  26. Perumal MB, Dhanasekaran S. Relaxin: A missing link in the pathomechanisms of systemic lupus erythematosus? Mod Rheumatol. 2014;24(4):547-551. https://doi.org/10.3109/ 14397595.2013.844297.
  27. Goldsmith LT, Weiss G, Palejwala S, et al. Relaxin regulation of endometrial structure and function in the rhesus monkey. Proc Natl Acad Sci U S A. 2004;101(13):4685-4689. https://doi.org/10.1073/pnas.0400776101.
  28. Hayes ES, Curnow EC, Trounson AO, et al. Implantation and pregnancy following in vitro fertilization and the effect of recombinant human relaxin administration in Macaca fascicularis. Biol Reprod. 2004;71(5):1591-1597. https://doi.org/10.1095/biolreprod.104.030585.

Supplementary files

Supplementary Files Action
1.
Fig. 1. Correlation between blood serum and follicular fluid relaxin levels and the studied parameters (* p < 0.05)

Download (449KB) Indexing metadata
2.
Fig. 2. a. Blood serum and follicular fluid relaxin levels with the use of gonadotropin preparations in the study groups; b. Blood serum and follicular fluid relaxin levels with the use of triggers of final oocyte maturation in the study groups (* p < 0.05)

Download (111KB) Indexing metadata
3.
Fig. 3. Two-dimensional graph of factorial loads of the studied indicators. Graph numbering: indicators associated with Factor 1: 2, follicular fluid relaxin level; 3, age; 4, blood serum anti-Müllerian hormone level; 7, body mass index; 9, day of puncture; 10, number of punctured follicles; 12, number of oocytes; 14, fertilization efficiency; indicators associated with Factor 2: 1, blood serum relaxin level; 5, blood serum luteinizing hormone level; 6, blood serum follicle-stimulating hormone level; 8, ∑ dose of gonadotropins; 11, endometrial thickness; 13, quality of oocytes; 15, number of blastocysts on day 5; 16, number of good quality embryos on day 5

Download (141KB) Indexing metadata

Statistics

Views

Abstract - 39

PDF (Russian) - 13

PDF (English) - 0

Cited-By


Article Metrics

Metrics Loading ...

PlumX

Dimensions


Copyright (c) 2020 Bespalova O.N., Zagaynova V.A., Kosyakova O.V., Gzgzyan A.M., Kogan I.Y., Milyutina Y.P., Tkachenko N.N., Borodina V.L., Lesik E.A., Mekina I.D., Komarova E.M.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies