Ovarian Hyper Stimulation Syndrome in Two Spontaneous Pregnancies


1 Department of Obstetrics and Gynecology, Faculty of Medicine, Khatamolanbia Hospital, Zahedan University of Medical Sciences, Zahedan, IR Iran

2 Women Health Research Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, IR Iran

3 Department of Infertility and IVF, Faculty of Medicine, Montaserieh Hospital, Mashhad University of Medical Sciences, Mashhad, IR Iran

4 School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran



Introduction: Ovarian hyper stimulation syndrome (OHSS) occurs mainly after excessive stimulation of the ovaries by exogenous gonadotropin administered in the context of ovulation induction and in vitro fertilization procedures (iatrogenic OHSS). Spontaneous OHSS is a rare event. Such cases would explain other etiologies except ovulation induction. In this case report, we have presented two cases of OHSS in spontaneously conceived pregnancies. Case Presentation: In this case report, we are going to present two cases of OHSS occurring in spontaneously conceived pregnancies. One of the patients mentioned the history of this syndrome in her sister, and the other one confronted with this syndrome in her second pregnancy. Both of them referred to the hospital with typical symptoms and signs of OHSS. They did not have Polycystic Ovary Syndrome (PCOS) and any other problem in pregnancy. Thrombophilia workup, Tumor markers, renin-aldosterone and thyroid function tests were normal. Discussion: The presence of OHSS in spontaneous pregnancy especially in familial pattern may lead us to evaluate some endogenous pathogenic factors.


  1. 1.Elchalal U, Schenker JG. The pathophysiology of ovarian hyperstimulation syndrome--views and ideas. Hum Reprod. 1997;12(6):1129–37.

    1. Schenker JG. Clinical aspects of ovarian hyperstimulation syndrome. Eur J Obstet Gynecol Reprod Biol. 1999;85(1):13–20.
    2. Whelan J3, Vlahos NF. The ovarian hyperstimulation syndrome. Fertil Steril. 2000;73(5):883–96.
    3. Goldsman MP, Pedram A, Dominguez CE, Ciuffardi I, Levin E, Asch RH. Increased capillary permeability induced by human follicular fluid: a hypothesis for an ovarian origin of the hyperstimulation syndrome. Fertil Steril. 1995;63(2):268–72.
    4. Levin ER, Rosen GF, Cassidenti DL, Yee B, Meldrum D, Wisot A, et al. Role of vascular endothelial cell growth factor in Ovarian Hyperstimulation Syndrome. J Clin Invest. 1998;102(11):1978–85.
    5. Delbaere A, Bergmann PJ, Gervy-Decoster C, Deschodt-Lanckman M, de Maertelaer V, Staroukine M, et al. Increased angiotensin II in ascites during severe ovarian hyperstimulation syndrome: role of early pregnancy and ovarian gonadotropin stimulation. Fertil Steril. 1997;67(6):1038–45.
    6. Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002;8(6):559–77.
    7. Vasseur C, Rodien P, Beau I, Desroches A, Gerard C, de Poncheville L, et al. A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome. N Engl J Med. 2003;349(8):753–9.
    8. Smits G, Olatunbosun O, Delbaere A, Pierson R, Vassart G, Costagliola S. Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor. N Engl J Med. 2003;349(8):760–6.
    9. Montanelli L, Delbaere A, Di Carlo C, Nappi C, Smits G, Vassart G, et al. A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome. J Clin Endocrinol Metab. 2004;89(4):1255–8.
    10. Cardoso CG, Graca LM, Dias T, Clode N, Soares L. Spontaneous ovarian hyperstimulation and primary hypothyroidism with a naturally conceived pregnancy. Obstet Gynecol. 1999;93(5 Pt 2):809–11.
    11. Edwards-Silva RN, Han CS, Hoang Y, Kao LC. Spontaneous ovarian hyperstimulation in a naturally conceived pregnancy with uncontrolled hypothyroidism. Obstet Gynecol. 2008;111(2 Pt 2):498–501. 13. Baba T, Endo T, Kitajima Y, Kamiya H, Moriwaka O, Saito T. Spontaneous ovarian hyperstimulation syndrome and pituitary adenoma: incidental pregnancy triggers a catastrophic event. Fertil Steril. 2009;92(1):390 e1–3.
    12. Ayhan A, Tuncer ZS, Aksu AT. Ovarian hyperstimulation syndrome associated with spontaneous pregnancy. Hum Reprod. 1996;11(8):1600–1.
    13. Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism. Am J Obstet Gynecol. 1989;160(5 Pt 1):1220–2.
    14. Zalel Y, Katz Z, Caspi B, Ben-Hur H, Dgani R, Insler V. Spontaneous ovarian hyperstimulation syndrome concomitant with spontaneous pregnancy in a woman with polycystic ovary disease. Am J Obstet Gynecol. 1992;167(1):122–4.
    15. Zalel Y, Orvieto R, Ben-Rafael Z, Homburg R, Fisher O, Insler V. Recurrent spontaneous ovarian hyperstimulation syndrome associated with polycystic ovary syndrome. Gynecol Endocrinol. 1995;9(4):313–5.
    16. Di Carlo C, Bruno P, Cirillo D, Morgera R, Pellicano M, Nappi C. Increased concentrations of renin, aldosterone and Ca125 in a case of spontaneous, recurrent, familial, severe ovarian hyperstimulation syndrome. Hum Reprod. 1997;12(10):2115–7.
    17. Strafford M, Moreno-Ruiz N, Stubblefield P. Ovarian hyperstimulation syndrome in a spontaneous pregnancy with a complete hydatidiform mole. Fertil Steril. 2009;92(1):395 e1–3.
    18. Ludwig M, Gembruch U, Bauer O, Diedrich K. Ovarian hyperstim- Mousavifar N et al. Razavi Int J Med. 2014;2(1):e14245 5 ulation syndrome (OHSS) in a spontaneous pregnancy with fetal and placental triploidy: information about the general pathophysiology of OHSS. Hum Reprod. 1998;13(8):2082–7.
    19. Delbaere A, Smits G, Olatunbosun O, Pierson R, Vassart G, Costagliola S. New insights into the pathophysiology of ovarian hyperstimulation syndrome. What makes the difference between spontaneous and iatrogenic syndrome? Hum Reprod. 2004;19(3):486–9.
    20. De Leener A, Montanelli L, Van Durme J, Chae H, Smits G, Vassart G, et al. Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology. J Clin Endocrinol Metab. 2006;91(2):555–62.
    21. Lipitz S, Grisaru D, Achiron R, Ben-Baruch G, Schiff E, Mashiach S. Spontaneous ovarian hyperstimulation mimicking an ovarian tumour. Hum Reprod. 1996;11(4):720–1.
    22. Rosen GF, Lew MW. Severe ovarian hyperstimulation in a spontaneous singleton pregnancy. Am J Obstet Gynecol. 1991;165(5 Pt 1):1312–3.
    23. Navot D, Margalioth EJ, Laufer N, Birkenfeld A, Relou A, Rosler A, et al. Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome. Fertil Steril. 1987;48(1):57–61.
    24. Jager W, Diedrich K, Wildt L. Elevated levels of CA-125 in serum of patients suffering from ovarian hyperstimulation syndrome. Fertil Steril. 1987;48(4):675–8.
    25. Murakami T, Higashitsuji H, Yoshinaga K, Terada Y, Ito K, Ikeda H. Management of ovarian hyperstimulation due to folliclestimulating hormone-secreting gonadotroph adenoma. BJOG. 2004;111(11):1297–300.
    26. Roberts JE, Spandorfer S, Fasouliotis SJ, Lin K, Rosenwaks Z. Spontaneous ovarian hyperstimulation caused by a folliclestimulating hormone-secreting pituitary adenoma. Fertil Steril. 2005;83(1):208–10.