Importance of estimation of follicular output rate (FORT) in females assisted by intracytoplasmic sperm injection
Keywords:
Intracytoplasmic sperm injection, Follicular output rate (FORT), Preovulatory follicle count, Antral follicle countAbstract
Background: We aimed to estimate pregnancy outcome after ICSI in terms of oocyte parameters, embryo quality, endometrial thickness, hormone and cytokine levels in women stratified on the basis of follicular output rate (FORT).
Methods: Quasi experimental design was carried out after approval from “Ethical review board of Islamabad clinic serving infertile couples” from July 2010 to August 2013. One thousand and fifty females were selected with the criteria of age between 21-40 years, infertility of more than 2 years, body mass index of 18-35 kg/m2, menstrual cycle of 25 ± 7 days, both ovaries present with normal uterine cavity, serum FSH levels less than 8 IU/ml and normal thyroid-stimulating hormone levels. Females on short agonist or antagonist protocol with diagnosis of polycystic ovarian syndrome, fibroids or in their male partner sperms retrieved by testicular biopsy were excluded from the study. Down regulation of ovaries was followed by controlled ovarian stimulation, Ovulation Induction (OI), oocyte pick up, in vitro fertilization, Embryo Transfer (ET) and confirmation of pregnancy was done by serum beta hCG of more than 25 mIU/ml and cardiac activity on trans vaginal scan. Enzyme linked immuno sorbent assay was used for peak and mid luteal estradiol (E2), progesterone (P) and interleukin I-β estimation on OI and ET days respectively. FORT (ratio of preovulatory follicle count to antral follicle count × 100 on OI day) stratified females into low under the 33rd percentile, medium between the 33rd and the 67th percentile and high above the 67th percentile. Characteristics of groups were compared by one way analysis of variance.
Results: Females 276 (33%), 288 (34%) and 282 (33%) comprised of low, medium and high FORT groups respectively. The number of retrieved, mature and fertilized oocytes, cleaved embryos, endometrial thickness and number of gestational sacs in the high FORT group was significantly high (P <0.001). High peak and midluteal E2 (P = 0.0025, 0.0001), low P (P = 0.0001) and high peak interleukin-1β (P = 0.0001) was observed in high FORT in comparison with medium FORT with resultant greater number of clinical pregnancies 183 (65%).
Conclusions: The FORT in non PCOS patients may reflect good reproductive outcome after ICSI with maximum clinical pregnancies in high FORT group.
References
Rijal B, Shrestha R, Jha B. Association of thyroid dysfunction among infertile women visiting infertility center of Om Hospital, Kathmandu, Nepal. Nepal Med Coll J. 2011;13(4):247-9.
Shaheen R, Fazil S, Sultan S, Subhan K, Tahir F. Prevalence of infertility in a cross section of Pakistani population. Pakistan J Zool. 2010;42(4):389-93.
Rehman R, Hussain Z, Zuberi NA. Prediction of success in intracytoplasmic sperm injection (ICSI) by estimation of serum estradiol/progesterone ratio on the day of embryo transfer. J Pak Med Assoc. 2013;63(5):609-13.
Rehman R, Hussain Z, Siddiq A. Role of progesterone in human embryo implantation. Rawal Med J. 2012;37(2):194-8.
Toporcerova S, Adam J, Toporcer T, Hredzak R, Ostro A. Basal concentrations of FSH (follicle stimulating hormone) as a transfer outcome. Hum Reprod. 2006;27(4):1066-72.
Arslan M, Bocca S, Mirkin S, Barroso G, Stadtmauer L, Oehninger S. Controlled ovarian hyperstimulation protocols for in vitro fertilization: two decades of experience after the birth of Elizabeth Carr. Fertil Steril. 2005;84:555-69.
Rehman R, Hussain Z, Fatima SS. Effect of weight status on pregnancy outcome in intra cytoplasmic sperm injection. Iran J Reprod Med. 2013;11(9):717-24.
Bancsi LF, Broekmans FJ, Looman CW, Habbema JD, Velde ER. Predicting poor ovarian response in IVF: use of repeat basal FSH measurement. J Reprod Med. 2004;49(3):187-94.
Broer SL, Mol BW, Hendriks D, Broekmans FJ. The role of antiMullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. Fertil Steril. 2009;91:705-14.
Melo MA, Garrido N, Alvarez C, Bellver J, Meseguer M, Pellicer A, et al. Antral follicle count (AFC) can be used in the prediction of ovarian response but cannot predict the oocyte/embryo quality or the in vitro fertilization outcome in an egg donation program. Fertil Steril. 2009;91:148-56.
Gallot V, Berwanger da Silva AL, Genro V, Grynberg M, Frydman N, Fanchin R. Antral follicle responsiveness to follicle-stimulating hormone administration assessed by the Follicular Output RaTe (FORT) may predict in vitro fertilization-embryo transfer outcome. Hum Reprod. 2012;27(4):1066-72.
Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17(2):121-55.
Guerif F, Lemseferr M, Blanchard M, Dominique Royere D. Top quality embryos at day 2: a prerequisite for single blastocyst transfer? An observational cohort study in women under 36. Assist Reprod Genet. 2009;26:443-9.
Kondapalli LA, Molinaro TA, Sammel MD, Dokras A. A decrease in serum estradiol levels after human chorionic gonadotrophin administration predicts significantly lower clinical pregnancy and live birth rates in in vitro fertilization cycles. Hum Reprod. 2012;27:2690-7.
Schoevers EJ, Kidson A, Verheijden JHM, Bevers MM. Effect of follicle-stimulating hormone on nuclear and cytoplasmic maturation of sow oocytes in vitro. Theriogenology. 2003;59(9):2017-28.
Aktan E, Bozkurt K, Ozer D, Yucebilgen S, Karadadas N, Bilgin O. The effect of mid luteal estradiol level on the outcome of ICSI-ET cycles. Arch Gynecol Obstet. 2004;269(2):134-8.
Faddy M. Follicle dynamics during ovarian ageing. Molecul Cellul Endocrinol. 2000;163(1-2):43-8.
Genro VK, Grynberg M, Scheffer JB, Roux I, Frydman R, Fanchin R. Serum anti-Mullerian hormone levels are negatively related to follicular output rate (FORT) in normo-cycling women undergoing controlled ovarian hyper stimulation. Hum Reprod. 2011;26:671-7.
Asimakopoulos B, Koster F, Felberbaum R, Al-Hasani S, Diedrich K, Nikolettos N. Cytokine and hormonal profile in blood serum and follicular fluids during ovarian stimulation with the multidose antagonist or the long agonist protocol. Hum Reprod. 2006;21(12):3091-5.
Luna M, Grunfeld L, Mukherjee T, Sandler B, Copperman AB. Moderately elevated levels of basal follicle-stimulating hormone in young patients predict low ovarian response, but should not be used to disqualify patients from attempting in vitro fertilization. Ferti Steril. 2007;87(4):782-7.
Jurema MW, Bracero NJ, Garcia JE. Fine tuning cycle day 3 hormonal assessment of ovarian reserve improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles. Fertil Steril. 2003;80(5):1156-61.
Phophong P, Ranieri DM, Khadum I, Meo F, Serhal P. Basal 17b-estradiol did not correlate with ovarian response and in vitro fertilization treatment outcome. Fertil Steril. 2000;74:1133-6.
Kassab A, Sabatini L, Lieberman G, Tozer A, Zosmer A, Davis C, et al. Does measuring early basal serum follicular luteinizing hormone assist in predicting in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) outcome? Reprod Biol Endocrinol. 2007;5:32.
Ottosen LD, Kesmodel U, Hindkjaer J, Ingerslev HJ. Pregnancy prediction models and eSET criteria for IVF patients: do we need more information? J Assist Reprod Genet. 2007;24:29-36.
Kara M, Tutlu K, Sofuoglu K, Devranoglu B, Cetinkaya T. Association between serum estradiol level on the hCG administration day and IVF-ICSI outcome. Iran J Reprod Med. 2012;10:53-8.
Rehman R, Hussain Z, Zahir H, Khan R. Impact of peak/mid luteal estradiol on pregnancy outcome after intracytoplasmic sperm injection. J Pak Med Assoc. 2014;64:780-4.
Rehman R, Jawaid S, Gul H, Khan R. Impact of peak estradiol levels on reproductive outcome of intracytoplasmic sperm injection. Pak J Med Sci. 2014;30(5):986-91.
Russell DL, Robker RL. Molecular mechanisms of ovulation: coordination through cumulus complex. Hum Reprod Update. 2007;13 289-312.
Blazer AS, Hogen JW, Frankfurter D, Hackett R, Keefe DL. Serum estradiol positively predicts outcome in patients undergoing in vitro fertilization. Fertil Steril. 2004;81(6):1707-9.
Ganesh A, Goswami S, Chattopadhyay R, Chakraborty C, Chaudhury K, Chakravarty BN. Luteal phase estradiol level: a potential predictive marker for successful pregnancy in in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2009;91:1018-22.
Fujimoto A, OsugaY, Fujiwara T, Yano T, Tsutsumi O, Momoeda M, et al. Human chorionic gonadotropin combined with progesterone for luteal support improves pregnancy rate in patients with low late-mid-luteal estradiol levels in IVF Cycles. J Assist Reprod Genet. 2002;19:550-4.
Jensen J, Lavy Y, Holzer H, Hurwitz A, Simon A, Revel A, et al. Young low responders protected from untoward effects of reduced ovarian response. Fertil Steril. 1998;69:1001-4.
Ou YC, Lan KC, Chang SY, Kung FT, Huang FJ. Increased progesterone/estradiol ratio on the day of HCG administration adversely affects success of in vitro fertilization-embryo transfer in patients stimulated with gonadotrophin-releasing hormone agonist and recombinant follicle-stimulating hormone. Taiwan J Obstet Gynecol. 2008;47:168-74.
Stravreus-Evers A, Nikas G, Sahlin L. Formation of pinopodes in human endometrium is associated with the concentrations of progesterone and progesterone receptors. Fertil Steril. 2001;76:782-91.
Mendoza C, Cremades N, Ruiz-Requena E, Martinez F, Ortega E, Bernabeu S, et al. Relationship between fertilization results after intracytoplasmic sperm injection, and intrafollicular steroid, pituitary hormone and cytokine concentrations. Hum Reprod. 1999;14(3):628-35.
Guzeloglu-Kayisli O, Basar M, Arici A. Basic aspects of implantation. Reprod Biomed Online. 2007;15(6):728-39.
Hanoch J, Lavy Y, Holzer H, Hurwitz A, Simon A, Revel A, et al. Young low responders protected from untoward effects of reduced ovarian response. Fertil Steril. 1998;69:1001-4.
Rehman R, Hussain Z, Faraz N. Effect of estradiol levels on pregnancy outcome in obese females. J Ayub Med Coll Abbottabad. 2012;24(3):3-5.
Zhang N, Hao CF, Zhuang LL, Liu XY, Gu HF, Liu S, et al. Prediction of IVF/ICSI outcome based on the follicular output rate (FORT). Reprod Bio Med Online. 2013;27(2):147-53.
Rinaldi L, Lisi F, Floccari A, Lisi R, Pepe G, Fishel S. Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection. Hum Reprod. 1996;11(7):1538-41.
Rehman R, Jawaid S, Hussain M, Katpar S, Baig M. Role of hormones and cytokines in creating an attractive endometrial bed for fertility: a quasi-study. Int J Recent Sci Res. 2014;5(7):1357-60.
