Biochemical predictors of ovarian hyperstimulation syndrome in women undergoing in vitro fertilization: a retrospective cohort study from a tertiary fertility center in Pakistan
DOI:
https://doi.org/10.18203/issn.2454-2156.IntJSciRep20263675Keywords:
Infertility, In vitro fertilization, Ovarian hyperstimulation syndrome, Biochemical predictors, PCOS, Pakistan, Low-middle-income countryAbstract
Background: Ovarian hyperstimulation syndrome (OHSS) is a rare but serious complication of controlled ovarian stimulation during assisted reproductive technology. This study identified biochemical predictors and described outcomes of OHSS among women undergoing in vitro fertilization (IVF) at a tertiary fertility center in Khyber-Pakhtunkhwa, Pakistan.
Methods: Records of 316 infertile women treated at the Center for Reproductive Medicine, Peshawar General Hospital, from December 2023 to December 2024 were reviewed. Patient characteristics, infertility diagnosis, treatment parameters, anti-Müllerian hormone (AMH), peak serum estradiol (E2), antral follicular count (AFC), and total oocytes retrieved were assessed. All patients received HCG Alpha 250 µg for final oocyte maturation. OHSS was classified using Golan and Weissman (2009) criteria. Analysis was performed using IBM SPSS Statistics v26.
Results: The mean age was 32.21±4.85 years and BMI 27.42±1.71 kg/m²; 69.6% had PCOS. Sixteen patients (5.06%) developed OHSS, all with PCOS as a contributing risk factor. 25.0% had moderate, 62.5% severe, and 12.5% had critical OHSS. Compared with non-OHSS patients, mean AFC (24 versus 13), AMH (6.5 versus 3.4 ng/ml), peak E2 (35 versus 18 ng/ml), and oocytes retrieved (15 versus 9) were higher. Nine (56.25%) achieved live birth, all after frozen embryo transfer.
Conclusions: AFC, AMH, peak serum estradiol, and total oocytes retrieved are the principal biochemical markers associated with OHSS in this Pakistani IVF cohort. The universal use of standard hCG triggering in a PCOS-predominant population represents the most modifiable contributor to the high severity distribution observed from low - and -middle income country centers.
Metrics
References
Ganer Herman H, Mizrachi Y, Horowitz E, Weissman A, Sabban B, Gluck O, et al. Obstetric outcomes following ovarian hyperstimulation syndrome in IVF: a comparison with uncomplicated fresh and frozen transfer cycles. BMC Pregnancy Childbirth. 2022;22(1):573. DOI: https://doi.org/10.1186/s12884-022-04903-9
Delvigne A, Dubois M, Battheu B, Bassil S, Meuleman C, De Sutter P, et al. The ovarian hyperstimulation syndrome in in-vitro fertilization: a Belgian multicentric study. II. Multiple discriminant analysis for risk prediction. Hum Reprod. 1993;8:1361-6. DOI: https://doi.org/10.1093/oxfordjournals.humrep.a138261
Aboulghar MA, Mansour RT. Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures. Hum Reprod Update. 2003;9(3):275-89. DOI: https://doi.org/10.1093/humupd/dmg018
Namavar Jahromi B, Parsanezhad ME, Shomali Z, Bakhshai P, Alborzi M, Vaziri NM, et al. Ovarian hyperstimulation syndrome: a narrative review of its pathophysiology, risk factors, prevention, classification, and management. Iran J Med Sci. 2018;43(3):248-60.
Golan A, Weissman A. A modern classification of OHSS. Reprod Biomed Online. 2009;19(1):28-32. DOI: https://doi.org/10.1016/S1472-6483(10)60042-9
Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002;8(6):559-77. DOI: https://doi.org/10.1093/humupd/8.6.559
Enskog A, Henriksson M, Unander M, Nilsson L, Brännström M. Prospective study of the clinical and laboratory parameters of patients in whom ovarian hyperstimulation syndrome developed during controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 1999;71:808-14. DOI: https://doi.org/10.1016/S0015-0282(99)00090-4
Tummon I, Gavrilova-Jordan L, Allemand MC, Session D. Polycystic ovaries and ovarian hyperstimulation syndrome: a systematic review. Acta Obstet Gynecol Scand. 2005;84:611-6. DOI: https://doi.org/10.1080/j.0001-6349.2005.00788.x
Teede HJ, Khomami MB, Morman R, Laven JSE, Joham AE, Costello MF, et al. Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process. Lancet. 2026;407(10545):2329-39. DOI: https://doi.org/10.1016/S0140-6736(26)00717-8
Delvigne A, Demoulin A, Smitz J, Donnez J, Koninckx P, Dhont M, et al. The ovarian hyperstimulation syndrome in in-vitro fertilization: a Belgian multicentric study. I. Clinical and biological features. Hum Reprod. 1993;8:1353-60. DOI: https://doi.org/10.1093/oxfordjournals.humrep.a138260
Navot D, Relou A, Birkenfeld A, Rabinowitz R, Brzezinski A, Margalioth EJ. Risk factors and prognostic variables in the ovarian hyperstimulation syndrome. Am J Obstet Gynecol. 1988;159:210-5. DOI: https://doi.org/10.1016/0002-9378(88)90523-6
Nakhuda GS, Chu MC, Wang JG, Sauer MV, Lobo RA. Elevated serum müllerian-inhibiting substance may be a marker for ovarian hyperstimulation syndrome in normal women undergoing in vitro fertilization. Fertil Steril. 2006;85:1541-3. DOI: https://doi.org/10.1016/j.fertnstert.2005.10.052
Asch RH, Li HP, Balmaceda JP, Weckstein LN, Stone SC. Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups. Hum Reprod. 1991;6:1395-9. DOI: https://doi.org/10.1093/oxfordjournals.humrep.a137276
Le Gouez A, Naudin B, Grynberg M, Mercier FJ. Ovarian hyperstimulation syndrome. Ann Fr Anesth Reanim. 2011;30(4):353-62. DOI: https://doi.org/10.1016/j.annfar.2010.11.026
Schirmer DA, Kulkarni AD, Zhang Y, Kawwass JF, Boulet SL, Kissin DM. Ovarian hyperstimulation syndrome after assisted reproductive technologies: trends, predictors, and pregnancy outcomes. Fertil Steril. 2020;114(3):567-78. DOI: https://doi.org/10.1016/j.fertnstert.2020.04.004
Vasseur C, Rodien P, Beau I, Desroches A, Gérard 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. DOI: https://doi.org/10.1056/NEJMoa030065
Zareen N. Management and obstetric outcome of ovarian hyperstimulation syndrome. J Coll Physicians Surg Pak. 2008;18(2):86-90.
World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-4. DOI: https://doi.org/10.1001/jama.2013.281053
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147(8):573-7. DOI: https://doi.org/10.7326/0003-4819-147-8-200710160-00010
Humaidan P, Nelson SM, Devroey P, Coddington CC, Schwartz LB, Gordon K, et al. Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials. Hum Reprod. 2016;31(9):1997-2004. DOI: https://doi.org/10.1093/humrep/dew149
Nastri CO, Teixeira DM, Moroni RM, Louzada VF, Martins WP. Ovarian hyperstimulation syndrome: pathophysiology, staging, prediction and prevention. Ultrasound Obstet Gynecol. 2015;45(4):377-93. DOI: https://doi.org/10.1002/uog.14684
Budev MM, Arroliga AC, Falcone T. Ovarian hyperstimulation syndrome. Crit Care Med. 2005;33(10):S301-6. DOI: https://doi.org/10.1097/01.CCM.0000182795.31757.CE
Devroey P, Polyzos NP, Blockeel C. An OHSS-free clinic by segmentation of IVF treatment. Hum Reprod. 2011;26(10):2593-7. DOI: https://doi.org/10.1093/humrep/der251
Papanikolaou EG, Pozzobon C, Kolibianakis EM, Camus M, Tournaye H, Fatemi HM, et al. Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles. Fertil Steril. 2006;85(1):112-20. DOI: https://doi.org/10.1016/j.fertnstert.2005.07.1292
Ferraretti AP, Gianaroli L, Magli MC, Fortini D, Selman HA, Felicini R. Elective cryopreservation of all pronucleate embryos in women at risk of ovarian hyperstimulation syndrome: efficiency and safety. Hum Reprod. 1999;14(6):1457-60. DOI: https://doi.org/10.1093/humrep/14.6.1457
Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634-47.
Tang H, Hunter T, Hu Y, Zhai SD, Sheng X, Hart RJ. Cabergoline for preventing ovarian hyperstimulation syndrome. Cochrane Database Syst Rev. 2012;2:CD008605. DOI: https://doi.org/10.1002/14651858.CD008605.pub2
Fiedler K, Ezcurra D. Predicting and preventing ovarian hyperstimulation syndrome (OHSS): the need for individualized not standardized treatment. Reprod Biol Endocrinol. 2012;10:32. DOI: https://doi.org/10.1186/1477-7827-10-32
Lensen SF, Wilkinson J, Leijdekkers JA, La Marca A, Mol BWJ, Marjoribanks J, et al. Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection. Cochrane Database Syst Rev. 2018;2(2):CD012693. DOI: https://doi.org/10.1002/14651858.CD012693.pub2
Humaidan P, Quartarolo J, Papanikolaou EG. Preventing ovarian hyperstimulation syndrome: guidance for the clinician. Fertil Steril. 2010;94(2):389-400. DOI: https://doi.org/10.1016/j.fertnstert.2010.03.028
Youssef MA, Al-Inany HG, Evers JL, Aboulghar M. Intra-venous fluids for the prevention of severe ovarian hyperstimulation syndrome. Cochrane Database Syst Rev. 2011;2:CD001302. DOI: https://doi.org/10.1002/14651858.CD001302.pub2
Broer SL, Dólleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Update. 2011;17(1):46-54. DOI: https://doi.org/10.1093/humupd/dmq034
La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, et al. Anti-Mullerian hormone (AMH) as a predictive marker in ART. Hum Reprod Update. 2010;16(2):113-30. DOI: https://doi.org/10.1093/humupd/dmp036
Lekamge DN, Barry M, Kolo M, Lane M, Gilchrist RB, Tremellen KP. Anti-Müllerian hormone as a predictor of IVF outcome. Reprod Biomed Online. 2007;14(5):602-10. DOI: https://doi.org/10.1016/S1472-6483(10)61053-X
Courbiere B, Oborski V, Braunstein D, Desparoir A, Noizet A, Gamerre M. Obstetric outcome of women with in vitro fertilization pregnancies hospitalized for ovarian hyperstimulation syndrome: a case-control study. Fertil Steril. 2011;95(5):1629-32. DOI: https://doi.org/10.1016/j.fertnstert.2010.12.015
Vloeberghs V, Peeraer K, Pexsters A, D'Hooghe T. Ovarian hyperstimulation syndrome and complications of ART. Best Pract Res Clin Obstet Gynaecol. 2009;23(5):691-709. DOI: https://doi.org/10.1016/j.bpobgyn.2009.02.006
Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21(4):411-26. DOI: https://doi.org/10.1093/humupd/dmv016
Mathur RS, Akande AV, Keay SD, Hunt LP, Jenkins JM. Distinction between early and late ovarian hyperstimulation syndrome. Fertil Steril. 2000;73(5):901-7. DOI: https://doi.org/10.1016/S0015-0282(00)00492-1
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Anum Ehsan, Fazia Raza, Nosheen Shams, F. N. U. Sawaira, Abdul B. Wardak, Ghulam M. Solangi

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