Effect of Anti-Zona Antibodies in Follicular Fluid and Serum on ICSI Outcomes For Explained and Unexplained Groups
Objective: This study aims to determine the presence of blood serum and follicular anti-zona pellucid antibody in two groups of sub-fertile women (explained and unexplained), to evaluate the influence of these autoantibodies on ICSI treatment outcomes and to interpret these findings according to the cause of subfertility treatment outcome.
Methods and Materials: This prospective cohort study included 45 sub-fertile women who are divided into subgroups; that are the explained and unexplained groups. All females underwent 45 IVF-ICSI cycles after a certain ovarian stimulation protocol, 45 reached the egg retrieval stage and 44 was reaching embryo transfer stage, at the Fertility center in AL-Najaf Al-Ashraf city from October 2015 to November 2016. Women had undergone thorough assessments (clinical history and full examination) and frequent ultrasonography with basal hormonal level in cycle day two and hematological assessment for AZA, hormonal assessments (E2), two days before retrieval. Also on the day of oocyte retrieval, follicular fluid was centrifuged and freeze for assessing AZA later. After 2 weeks, serum assessed for HCG to detect biochemical pregnancy.
Results: The study found that the age mean and range of the studied groups were (29.71±6.62) (18-45year); the BMI mean was (27.70±4.05) Kg/m2, ranged between (19 -35.7); and duration of infertility in years (8.40±4.16), ranged between (2-18) years, and a large percent of them had a history of primary subfertility (86.7%). Regarding the cause of subfertility, a high percent of the studied groups of unexplained cause with a percentage (40%). Regarding ICSI outcome, the pregnancy rate was 28.89%. In women with unexplained cause, pregnancy rate was (33.30%) followed by women with explained cause which was (25.90%). Pregnant women had better ICSI parameters than non-pregnant one. Basal hormonal levels were within normal range, also peak E2 show normal value, but E2 at CD2 was of higher significance in an unexplained type or group. Follicular and serum AZA was higher in women with unexplained cause than in women with explained cause but of no significant difference. Furthermore, peak mean of Follicular AZA in women with unexplained infertility was (10.29 IU/L), followed by ovulatory cause. Pregnancy rate in women with high AZA decreased, and it affect ICSI outcome in general. Regarding FF –AZA, higher follicular fluid values were in unexplained cause. Also, positive non-significant correlation between E2 and follicle count with serum AZA was observed. Finally, there were some correlations between blood serum AZA, FF AZA and ICSI outcome and other parameters.
Conclusion: We conclude from this study that multiple factors affect ICSI outcome, and may be used as markers of fecundity for counseling IVF/ICSI candidates to elevate success rate and decrease the cancellation cycles. Women with unexplained subfertility must firstly be checked for presence of AZA and treated before beginning ICSI cycle to increase conception rate. Minimal immune activation as detected by serum and follicular AZA may help in success rate of ICSI outcome.
-Wasiu Eniola O., Adebayo Adetola A. and Taiwo Abayomi B., 2012. A review of female infertility: important etiological factors and management. J Microbiol Biotech Res, 2(3): 379-385.
-Saito S., 2000. “ Cytokine network at the feto-maternal interface,” Journal of Reproductive Immunology, vol. 47, no. 2, pp. 87–103.
-Thellin O., Coumans B., Zorzi W., Igout A. and Heinen E., 2000. “ Tolerance to the foeto- placental ‘graft’: ten ways to support a child for nine months,” Current Opinion in Immunology, vol.12, no. 6, pp. 731–737.
-Reimand K., Talja I., Metsküla K., Kadastik Ü., Matt K. and Uibo R., 2001. Autoantibody studies of female patients with reproductive failure. Journal of Reproductive Immunology. 51(2): 167–176.
-Forges T., Barbarino- Monnier P., Faure G.C., and B´en´e M. C., 2004. “Autoimmunity and antigenic targets in ovarian pathology,” Human Reproduction Update, vol. 10, no. 2, pp. 163–175.
-Luborsky J., 2002. “Ovarian autoimmune disease and ovarian autoantibodies,” Journal of Women’s Health and Gender-Based Medicine, vol. 11, no. 7, pp. 585–599.
-Raivo Uibo,1, 2 Andres Salumets,2, 3 and Gilbert Faure, 2012. Immunological Aspects of Human Reproduction.
-Cho J. H. & Gregersen P. K., 2011. Genomics and the multi factorial nature of human autoimmune disease. N. Engl. J. Med. 365, 1612–1623.
-Jasani B. et al., 1999. Natural antibody status in patients with Hashimoto’s thyroiditis. J. Clin. Lab. Immunol. 51, 9–20.
-Tagoe C. E., Zezon A. and Khattri S., 2012. Rheumatic manifestations of autoimmune thyroid disease: the other autoimmune disease. J. Rheumatol.39, 1125–1129.
-Gleicher N., 1999. Reproductive failure prior to the onset of clinical autoimmune disease. Rheumatology (Oxford) 38, 485–487.
-Takamizawa S., Shibahara H., Shibayama T., Suzuki M., 2007. Detection of antizona pellucida antibodies in the sera from premature ovarian failure patients by a highly specific test. Fertil. Steril. 88, 925–932.
-Nishimoto T., Mori T., Yamada I. and Nishimura T., 1980. Auto antibodies to zona pellucida in infertile and aged women. Fertil Steril., Dec; 34(6):5526.
-Shivers CA. and Dunbar BS., 1977. Autoantibodies to the Zona pellucida: A possible cause for infertility in women. Science; 197:1082-1086.
-Ulcova- Gallova Z., Babcova K., Novakova P., Micanova Z., Rokyta Z. , 2004. Anti-zonal antibodies in ovulatory cervical mucus and in serum of patients with fertility disorders, Ceska Gynekol., May; 69(3): 215-8.
-Kamada M., Daitoh T., Mori K., Maeda N., Hirano K., Irahara M., Aono T. and Mori T., 1992. Etiological implication of auto antibodies to zona pellucida in human female infertility. Am J Reprod Immunol, Sep; 28(2):104-9.
-Luborsky J., Llanes B., Davies S., Binor Z., Radwanska E.,and Pong R., 1999. “ Ovarian autoimmunity: greater frequency of autoantibodies in premature menopause and unexplained infertility than in the general population,” Clinical Immunology, vol. 90, no. 3, pp.368–374.
-Hovav Y., Almagor M., Benbenishti D., Margalioth EJ., Kafka I., Yaffe H., 1994. Immunity to zona pellucida in women with low response to ovarian stimulation, in unexplained infertility and after multiple IVF attempts. Hum Reprod, Apr;9(4):643-5.
-Dunbar BS., Avery S., Lee V., Prasad S., Schwahn D., Schwoebel E., Skinner S., Wilkins B., 1994. The mammalian zona pellucida: its biochemistry, immunochemistry, molecular biology, and developmental expression. Reprod. Fertil Dev.; 6(3):331-47.
-De Vos A., 2000. Intra-cytoplasmic sperm injection (ICSI). Hum Reprod, 15(4): 59-64.
-Huang JYJ. and Rosenwaks Z., 2012. In vitro fertilization treatment and factors affecting success. Best Pract Res Clinical Obestet and Gynecol, 26: 777-788.
-WHO Expert Consultation., 2004. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. The Lancet, 363(9403): 157-163.
-Badawy A., Wageah A., El Gharib M. and Osman EE., 2011. Prediction and diagnosis of poor ovarian response: The dilemma. J Reprod Infertil, 12(4): 241-248.
-Elder K. and Dale B., 2011. Micromanipulation techniques In: Text book of In-Vitro Fertilization. This 3rd edition published by Cambridge University Press, Ch.13, P.2116.
-Elder K. and Dale B., 2011. Endocrine control of reproduction -Controlled ovarian hyper-stimulation for ART. In: In-Vitro Fertilization. 3rd edition. Elder K and Dale B. (eds.), Cambridge: 19-26.
-Al-Taee H., Al-Khfaji Z. and Al-Madfai Z., 2014. The Role of Ovarian Reserve Tests in predicting Intra-Cytoplasmic Sperm Injection Cycles Outcome. Asian J of Pharma, Nurs and Med Sci, 2(1): 15-23.
-Daniel WW., 1999. Probability and distribution biostatistics. In: A foundation for analysis in health science. 7th edition. Daniel WW. (ed.), John willey and Sons, INC-USA: 83-123.
-Gleicher N., El-Roeiy A., Confino E., and Friberg J., 1989. “Reproductive failure because of auto antibodies: unexplained infertility and pregnancy wastage,” American Journal of Obstetrics and Gynecology, vol. 160, no. 6, pp. 1376–1380.
-Czuppon AB., Dietl J. and Tripatzis I., 1987. Solid-phase antigen immunoassay for the detection of anti-zona pellucida antibodies in clinically defined sera. J Clin Chem Clin Biochem; 25:87–90.
- El-Roeiy A., Gleicher N., Friberg J., Confino E. and Dudkiewicz A.,1987. Correlation between peripheral blood and follicular fluid autoantibodies and impact on in vitro fertilization. Obstet Gynecol; 70:163–170.
- Singh J., Mhaskar AM., 1985. Enzyme-linked immune sorbent determination of auto antibodies to zona pellucid as a possible cause of infertility in women. J Immunol Methods;79: 133– 141.
- Farquhar C.; Rishworth J. R.; Brown J.; Nelen W. L. M.; Marjoribanks J., 2013. Brown, Julie, ed. "Assisted reproductive technology: an overview of Cochrane Reviews".
- Stolwijk AM., Wetzels AM. and Braat DD., 2000. Cumulative probability of achieving an ongoing pregnancy after in-vitro fertilization and intra-cytoplasmic sperm injection according to a woman’s age, subfertility diagnosis and primary or secondary subfertility. Hum Reprod;15: 203–9.
- Check ML., Yuan W., Check JH., Swenson K., Lee G. and Choe JK., 2002. Cumulative probability of pregnancy following IVF with ICSI and fresh or frozen embryo transfer. Arch Androl.; 48:5–7.
- Olivius K., Friden B., Lundin K. and Bergh C., 2002. Cumulative probability of live birth after three in vitro fertilization /intra-cytoplasmic sperm injection cycles. Fertil Steril;77: 505–10.
-Orvieto R., Chen R., Ashkenazi J., Ben-Harush A., Bar J. and Fisch B., 2004a. C-reactive protein levels in patients undergoing controlled ovarian hyper-stimulation for IVF cycle. Hum Reprod; 19:357–9.
-Orvieto R., 2004b. Controlled ovarian hyper-stimulation-an inflammatory state. J Soc Gynecol Investig 11,424–426.
- Arefi S., Babashamsi M., Panahi P.S., Saruiy L.A. and Zeraati H., 2010. C-reactive protein level and pregnancy rate in patients undergoing IVF/ICSI. Iranian Journal of Reproductive Medicine Vol.8. No.4. pp: 197-202.
Copyright (c) 2019 University of Thi-Qar Journal Of Medicine
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.