Cleavage and Blastocyst Formation Rates and Their Correlation with Fertilization Outcomes in Natural Versus Programmed IVF Cycles: A Randomized Clinical Trial
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Abstract
Background: Early embryo developmental milestones, particularly cleavage and blastocyst formation, are important indicators of embryo competence in in-vitro fertilization (IVF). Whether menstrual cycle programming with combined oral contraceptive pills (OCPs) alters these embryological outcomes compared with natural cycles remains a subject of debate, especially in low- and middle-income settings.
Objective: To compare cleavage and blastocyst formation rates in natural versus OCP-programmed IVF cycles and to evaluate their relationship with fertilization outcomes.
Methods: This single-center, open-label randomized clinical trial enrolled 86 women undergoing IVF at a tertiary fertility center in Nigeria. Participants were randomized equally to undergo controlled ovarian stimulation either in a natural cycle or following OCP pretreatment. Standardized stimulation, fertilization (IVF or ICSI), and embryo culture protocols were used in both groups. Cleavage rate and blastocyst formation rate were the primary outcomes, while correlations between fertilization rate and subsequent embryo development were secondary outcomes. Data were analyzed using intention-to-treat principles.
Results: There was no statistically significant difference between the OCP-programmed and natural cycle groups in mean cleavage rate (70.7% vs. 67.2%, p = 0.438) or blastocyst formation rate (52.4% vs. 45.2%, p = 0.122). Fertilization rate demonstrated a strong positive correlation with cleavage rate (r = 0.758, p < 0.001) and a moderate correlation with blastocyst formation rate (r = 0.659, p < 0.001). Cleavage rate was also moderately correlated with blastocyst development (r = 0.515, p < 0.001).
Conclusion: Cycle programming with combined oral contraceptive pills does not adversely affect cleavage or blastocyst formation in IVF. Fertilization success strongly influences subsequent embryo development irrespective of cycle type. These findings support the use of OCP pretreatment for scheduling flexibility without compromising early embryological outcomes.
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References
I. World Health Organization. Infertility definitions and terminology. Geneva: WHO; 2014.
II. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9(12):e1001356.
III. Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011;26(7):1768–74.
IV. Alpha Scientists in Reproductive Medicine, ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270–83.
V. Gardner DK, Schoolcraft WB. In vitro culture of human blastocysts. In: Jansen R, Mortimer D, editors. Towards Reproductive Certainty: Fertility and Genetics Beyond 1999. Carnforth: Parthenon Press; 1999. p. 378–88.
VI. Blake DA, Proctor M, Johnson NP. The merits of blastocyst versus cleavage stage embryo transfer: a Cochrane review. Hum Reprod. 2004;19(4):795–807.
VII. Hardarson T, Van Landuyt L, Jones G. The blastocyst. Hum Reprod. 2012;27(Suppl 1):i72–91.
VIII. Griesinger G, Kolibianakis EM, Venetis CA, Diedrich K, Tarlatzis B. Oral contraceptive pill pretreatment in ovarian stimulation with GnRH antagonists for IVF: a systematic review and meta-analysis. Fertil Steril. 2008;90(4):1055–63.
IX. Fatemi HM, Popovic-Todorovic B, Humaidan P, Kol S, Banker M, Devroey P. An update of luteal phase support in stimulated IVF cycles. Hum Reprod Update. 2007;13(6):581–90.
X. Kolibianakis EM, Venetis CA, Papanikolaou EG, Tarlatzis BC. Oral contraceptive pretreatment and IVF outcome: a systematic review. Hum Reprod Update. 2006;12(2):123–36.
XI. Pelinck MJ, Vogel NE, Hoek A, Arts EG, Simons AH, Heineman MJ. Minimal stimulation IVF: a randomized controlled trial comparing minimal stimulation IVF with conventional IVF. Hum Reprod. 2008;23(5):940–8.
XII. Griesinger G, Diedrich K, Tarlatzis BC, Kolibianakis EM. GnRH-antagonists in ovarian stimulation for IVF in normal responders: a meta-analysis. Hum Reprod Update. 2006;12(3):259–73.
XIII. Kolibianakis EM, Collins J, Tarlatzis BC, Devroey P. Are oral contraceptives needed before IVF? Reprod Biomed Online. 2012;24(2):146–54.
XIV. Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles. Hum Reprod Update. 2013;19(5):433–57.
XV. Abayomi O, Ajayi AB, Akinola OI, Akande VA. Assisted reproductive technology in sub-Saharan Africa: current practice and challenges. Int J Gynaecol Obstet. 2020;150(2):147–54.
XVI. Bosch E, Labarta E, Crespo J, Simón C. Impact of oral contraceptive pretreatment on ovarian stimulation for IVF. Fertil Steril. 2010;93(5):1559–1566.
XVII. Kim Y, Koo HS, Lee JR, et al. Effects of oral contraceptive pretreatment on embryo quality and IVF outcomes. Reprod Biomed Online. 2012;24(2):143–150.
XVIII. Griesinger G, Diedrich K, Devroey P, et al. Oral contraceptive pill pretreatment before ovarian stimulation: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):338–346.
XIX. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11(3):307–311.
XX. Rienzi L, Gracia C, Maggiulli R, et al. Predictive value of fertilization rate and embryo development for IVF outcomes. Hum Reprod. 2011;26(8):2044–2051.
XXI. Alpha Scientists in Reproductive Medicine. Istanbul consensus workshop on embryo assessment: proceedings. Hum Reprod. 2011;26(6):1270–1283.
XXII. Gardner DK, Lane M. Culture and transfer of human blastocysts: a practical guide. Hum Reprod Update. 1997;3:271–281.
XXIII. Humaidan P, Bredkjaer HE, Bungum L, et al. Impact of oral contraceptive pill pretreatment on controlled ovarian stimulation. Fertil Steril. 2007;88(1):120–127.
XXIV. Macklon NS, Stouffer RL, Giudice LC, Fauser BC. The science behind 25 years of IVF. Nat Rev Endocrinol. 2006;2:1–12.