Abstract
Objective
To investigate how the mode of conception affects maternal relaxin, creatinine, and electrolyte concentrations.
Background
Pregnancies achieved by fertility treatment often begin in a nonphysiologic endocrine milieu with no corpus luteum (CL) or with many corpora lutea. The CL produces not only estradiol and progesterone but is also the sole source of relaxin in early pregnancy, a hormone that may contribute to maternal systemic and renal vasodilation. There is limited data about maternal physiology in early pregnancy during fertility treatment, and studies have rarely considered the potential effect of the absence of the CL. To begin to address this gap in knowledge, we sought to investigate how the mode of conception affects maternal relaxin, creatinine, and electrolyte concentrations.
Methods
One hundred eighty-four women who received care at an academic infertility practice provided serum samples. Levels of relaxin 2, creatinine, and electrolytes were compared between 4 groups defined on the basis of mode of conception which corresponded to categories of CL number: (1) absence of the CL, (2) single CL, (3) multiple CL from ovarian stimulation not including in vitro fertilization (IVF), and (4) multiple CL from IVF with fresh embryo transfer.
Results
Relaxin-2 levels were undetectable in patients lacking a CL. Creatinine, sodium, and total CO2 levels were significantly higher in the 0 CL group (relaxin absent) compared to all other groups (relaxin present). Compared to clomiphene, use of letrozole was associated with a lower relaxin level.
Conclusion
Early creatinine and sodium concentrations are increased in the absence of relaxin. Given the increasing utilization of frozen embryo transfer, further studies comparing programmed with natural cycles are warranted.
Similar content being viewed by others
References
Chapman AB, Abraham WT, Zamudio S, et al. Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int. 1998;54(6):2056–2063.
Petersen JW, Liu J, Chi YY, et al. Comparison of multiple non-invasive methods of measuring cardiac output during pregnancy reveals marked heterogeneity in the magnitude of cardiac output change between women. Physiol Rep. 2017;5(8):1–11.
Capeless EL, Clapp JF. Cardiovascular changes in early phase of pregnancy. Am J Obstet Gynecol. 1989;161(6 pt 1):1449–1453.
Robson SC, Hunter S, Boys RJ, Dunlop W. Serial study of factors influencing changes in cardiac output during human pregnancy. Am J Physiol. 1989;256(4 pt 2):H1060–H1065.
Chapman AB, Zamudio S, Woodmansee W, et al. Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle mimic early pregnancy. Am J Physiol. 1997;273(5 pt 2):F777–F782.
Smith MC, Murdoch AP, Danielson LA, Conrad KP, Davison JM. Relaxin has a role in establishing a renal response in pregnancy. Fertil Steril. 2006;86(1):253–255.
Novak J, Danielson LA, Kerchner LJ, et al. Relaxin is essential for renal vasodilation during pregnancy in conscious rats. J Clin Invest. 2001;107(11):1469–1475.
Debrah DO, Novak J, Matthews JE, Ramirez RJ, Shroff SG, Conrad KP. Relaxin is essential for systemic vasodilation and increased global arterial compliance during early pregnancy in conscious rats. Endocrinology. 2006;147(11):5126–5131.
Conrad KP. Maternal vasodilation in pregnancy: the emerging role of relaxin. Am J Physiol Regul Integr Comp Physiol. 2011;301(2):R267–R275.
Emmi AM, Skurnick J, Goldsmith LT, et al. Ovarian control of pituitary hormone secretion in early human pregnancy. J Clin Endocrinol Metab. 1991;72(6):1359–1369.
Conrad KP, Baker VL. Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies. Am J Physiol Regul Integr Comp Physiol. 2013;304(2):R69–R72.
Zhu L, Zhang Y, Liu Y, et al. Maternal and live-birth outcomes of pregnancies following assisted reproductive technology: a retrospective cohort study. Sci Rep. 2016;6:35141.
Storgaard M, Loft A, Bergh C, et al. Obstetric and neonatal complications in pregnancies conceived after oocyte donation: a systematic review and meta-analysis. BJOG. 2017;124(4):561–572.
Sites CK, Wilson D, Barsky M, et al. Embryo cryopreservation and preeclampsia risk. Fertil Steril. 2017;108(5):784–790.
Chen ZJ, Shi Y, Sun Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375(6):523–533.
Wong KM, van Wely M, Mol F, Repping S, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2017;3:CD011184.
Johnson MR, Okokon E, Collins WP, Sharma V, Lightman SL. The effect of human chorionic gonadotropin and pregnancy on the circulating level of relaxin. J Clin Endocrinol Metab. 1991;72(5):1042–1047.
Haning RV Jr, Goldsmith LT, Seifer DB, et al. Relaxin secretion in in vitro fertilization pregnancies. Am J Obstet Gynecol. 1996;174(1 pt 1):233–240.
Mushayandebvu TI, Goldsmith LT, Von Hagen S, Santoro N, Thurston D, Weiss G. Elevated maternal serum relaxin concentrations throughout pregnancy in singleton gestations after superovulation. Obstet Gynecol. 1998;92(1):17–20.
Johnson MR, Abdalla H, Allman AC, Wren ME, Kirkland A, Lightman SL. Relaxin levels in ovum donation pregnancies. Fertil Steril. 1991;56(1):59–61.
DiMagno EP, Corle D, O’Brien JF, Masnyk IJ, Go VL, Aamodt R. Effect of long-term freezer storage, thawing, and refreezing on selected constituents of serum. Mayo Clin Proc. 1989;64(10):1226–1234.
Gislefoss RE, Grimsrud TK, Morkrid L. Long-term stability of serum components in the Janus Serum Bank. Scand J Clin Lab Invest. 2008;68(5):402–409.
Kale VP, Patel SG, Gunjal PS, et al. Effect of repeated freezing and thawing on 18 clinical chemistry analytes in rat serum. J Am Assoc Lab Anim Sci. 2012;51(4):475–478.
Stoelk E, Chegini N, Lei ZM, Rao CV, Bryant-Greenwood G, Sanfilippo J. Immunocytochemical localization of relaxin in human corpora lutea: cellular and subcellular distribution and dependence on reproductive state. Biol Reprod. 1991;44(6):1140–1147.
Sherwood OD. Relaxin’s physiological roles and other diverse actions. Endocr Rev. 2004;25(2):205–234.
Khan-Dawood FS, Goldsmith LT, Weiss G, Dawood MY. Human corpus luteum secretion of relaxin, oxytocin, and progesterone. J Clin Endocrinol Metab. 1989;68(3):627–631.
Johnson MR, Abdalla H, Allman AC, Wren ME, Kirkland A, Lightman SL. Relaxin levels in ovum donation pregnancies. Fertil Steril. 1991;56(1):59–61.
Sherwood O. Relaxin. In: Knobil E, Neill J, Greenwald GS, et al., eds. The Physiology of Reproduction. New York, NY: Raven; 1994:861–1009.
Stewart DR, Celniker AC, Taylor CA Jr, Cragun JR, Overstreet JW, Lasley BL. Relaxin in the peri-implantation period. J Clin Endocrinol Metab. 1990;70(6):1771–1773.
Quagliarello J, Szlachter N, Steinetz BG, Goldsmith LT, Weiss G. Serial relaxin concentrations in human pregnancy. Am J Obstet Gynecol. 1979;135(1):43–44.
Quagliarello J, Goldsmith L, Steinetz B, Lustig DS, Weiss G. Induction of relaxin secretion in nonpregnant women by human chorionic gonadotropin. J Clin Endocrinol Metab. 1980;51(1):74–77.
Gagliardi CL, Goldsmith LT, Saketos M, Weiss G, Schmidt CL. Human chorionic gonadotropin stimulation of relaxin secretion by luteinized human granulosa cells. Fertil Steril. 1992;58(2):314–320.
Arthur ID, Anthony FW, Adams S, Thomas EJ. Serum relaxin and the major endometrial secretory proteins in in-vitro fertilization and down-regulated hormone-supported and natural cycle frozen embryo transfer. Hum Reprod. 1996;11(1):88–91.
Mok-Lin E, Brauer AA, Schattman G, Zaninovic N, Rosenwaks Z, Spandorfer S. Follicular flushing and in vitro fertilization outcomes in the poorest responders: a randomized controlled trial. Hum Reprod. 2013;28(11):2990–2995.
Jeyabalan A, Conrad KP. Renal physiology and pathophysiology in pregnancy. Renal and Electrolyte Disorders. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010:462–518.
Davison JM, Gilmore EA, Durr J, Robertson GL, Lindheimer MD. Altered osmotic thresholds for vasopressin secretion and thirst in human pregnancy. Am J Physiol. 1984;246(1 pt 2):F105–F109.
Haning RV Jr, Canick JA, Goldsmith LT, Shahinian KA, Erinakes NJ, Weiss G. The effect of ovulation induction on the concentration of maternal serum relaxin in twin pregnancies. Am J Obstet Gynecol. 1996;174(1 pt 1):227–232.
Danielson LA, Sherwood OD, Conrad KP. Relaxin is a potent renal vasodilator in conscious rats. J Clin Invest. 1999;103(4):525–533.
Conrad KP, Debrah DO, Novak J, Danielson LA, Shroff SG. Relaxin modifies systemic arterial resistance and compliance in conscious, nonpregnant rats. Endocrinology. 2004;145(7):3289–3296.
Smith MC, Danielson LA, Conrad KP, Davison JM. Influence of recombinant human relaxin on renal hemodynamics in healthy volunteers. J Am Soc Nephrol. 2006;17(11):3192–3197.
Easterling TR, Benedetti TJ, Schmucker BC, Millard SP. Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol. 1990;76(6):1061–1069.
Bosio PM, McKenna PJ, Conroy R, O’Herlihy C. Maternal central hemodynamics in hypertensive disorders of pregnancy. Obstet Gynecol. 1999;94(6):978–984.
Weisinger RS, Burns P, Eddie LW, Wintour EM. Relaxin alters the plasma osmolality-arginine vasopressin relationship in the rat. J Endocrinol. 1993;137(3):505–510.
Brunton PJ, Russell JA. Endocrine induced changes in brain function during pregnancy. Brain Res. 2010;1364:198–215.
Wenner MM, Stachenfeld NS. Blood pressure and water regulation: understanding sex hormone effects within and between men and women. J Physiol. 2012;590(23):5949–5961.
Author information
Authors and Affiliations
Corresponding author
Additional information
Authors’ Note
Frauke von Versen-Höynck and Nairi K. Strauch consider that the first two authors should be regarded as joint First Authors. The work reported was done at Stanford University and University of Florida.
Rights and permissions
About this article
Cite this article
von Versen-Höynck, F., Strauch, N.K., Liu, J. et al. Effect of Mode of Conception on Maternal Serum Relaxin, Creatinine, and Sodium Concentrations in an Infertile Population. Reprod. Sci. 26, 412–419 (2019). https://doi.org/10.1177/1933719118776792
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719118776792