Prognostic Factors Associated with Clinical Pregnancy in in Vitro Fertilization Using Pituitary Down-regulation with Depot and Daily Low-dose Luteal Phase Gonadotropin Releasing Hormone Agonists: A Single Center's Experience

Overview

Journal J Hum Reprod Sci

Date 2015 Apr 4

PMID 25838746

Citations 6

Authors

Caiyun Liao

Rui Huang

Roberta W Scherer

Xiao-Yan Liang

Affiliations

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Abstract

Aim: To review the experience on depot-dose, and daily low-dose gonadotropin releasing hormone agonist (GnRHa) long protocols and identify prognostic factors.

Setting And Design: A chart review was conducted on 2106 depot and 1299 daily low-dose cycles at a university hospital.

Methods: Clinical parameters were summarized, and prognostic factors of clinical pregnancy for each protocol were identified by logistic regressions. Missing data were imputed using multiple imputations (MI) and the regression models were rerun after MI.

Results: Clinical pregnancy rate was 57.5% and 46.9% in the depot and daily low-dose groups, respectively. Logistic regressions with MI identified age (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92-0.98), serum progesterone (OR: 0.62, 95% CI: 0.45-0.84) and endometrial thickness (OR: 1.06, 95% CI: 1.02-1.12) on human chorionic gonadotropin (hCG) day, number of oocytes retrieved (OR: 1.04, 95% CI: 1.01-1.06), fertilization rate (OR: 2.66, 95% CI: 1.46-4.87) and ratio of good-quality D3 embryos (OR: 4.31, 95% CI: 2.79-6.67) as prognostic factors in the depot group. Age (OR: 0.95, 95% CI: 0.92-0.98), endometrial thickness on hCG day (OR: 1.09, 95% CI: 1.03-1.15), ratio of good quality D3 embryos (OR: 2.56, 95% CI: 1.59-4.13) and the number of cryopreserved embryos (OR: 1.07, 95% CI: 1.003-1.15) are prognostic for the daily low-dose protocol. Some regression coefficients that are significant under model-wise deletion become nonsignificant after MI.

Conclusions: Age, embryo quality and endometrial thickness on hCG day are important prognostic factors for both 1.0/1.3 mg depot and 0.05/0.1 mg daily low-dose luteal phase GnRHa long protocols. MI is a valuable tool to gauge and address bias caused by missing data in reproductive medicine.

Citing Articles

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References

Cai Q, Wan F, Huang R, Zhang H . Factors predicting the cumulative outcome of IVF/ICSI treatment: a multivariable analysis of 2450 patients. Hum Reprod. 2011; 26(9):2532-40. DOI: 10.1093/humrep/der228. View

Lahoud R, Kwik M, Ryan J, Al-Jefout M, Foley J, Illingworth P . Elevated progesterone in GnRH agonist down regulated in vitro fertilisation (IVFICSI) cycles reduces live birth rates but not embryo quality. Arch Gynecol Obstet. 2011; 285(2):535-40. DOI: 10.1007/s00404-011-2045-0. View

Dal Prato L, Borini A, Cattoli M, Bonu M, Sereni E, Flamigni C . GnRH analogs: depot versus short formulations. Eur J Obstet Gynecol Reprod Biol. 2004; 115 Suppl 1:S40-3. DOI: 10.1016/j.ejogrb.2004.01.014. View

Van Vaerenbergh I, Van Lommel L, Ghislain V, Int Veld P, Schuit F, Fatemi H . In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression. Hum Reprod. 2009; 24(5):1085-91. DOI: 10.1093/humrep/den501. View

Huang R, Fang C, Xu S, Yi Y, Liang X . Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles. Fertil Steril. 2012; 98(3):664-670.e2. DOI: 10.1016/j.fertnstert.2012.05.024. View

Fleming R, LLOYD F, Herbert M, Fenwick J, Griffiths T, Murdoch A . Effects of profound suppression of luteinizing hormone during ovarian stimulation on follicular activity, oocyte and embryo function in cycles stimulated with purified follicle stimulating hormone. Hum Reprod. 1998; 13(7):1788-92. DOI: 10.1093/humrep/13.7.1788. View

Taranissi M, El-Toukhy T, Gorgy A, Verlinsky Y . Influence of maternal age on the outcome of PGD for aneuploidy screening in patients with recurrent implantation failure. Reprod Biomed Online. 2005; 10(5):628-32. DOI: 10.1016/s1472-6483(10)61670-7. View

Gardner D, Lane M, Stevens J, Schlenker T, Schoolcraft W . Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000; 73(6):1155-8. DOI: 10.1016/s0015-0282(00)00518-5. View

Labarta E, Martinez-Conejero J, Alama P, Horcajadas J, Pellicer A, Simon C . Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011; 26(7):1813-25. DOI: 10.1093/humrep/der126. View

10.

Bosch E, Labarta E, Crespo J, Simon C, Remohi J, Jenkins J . Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles. Hum Reprod. 2010; 25(8):2092-100. DOI: 10.1093/humrep/deq125. View

11.

Racowsky C, Ohno-Machado L, Kim J, Biggers J . Is there an advantage in scoring early embryos on more than one day?. Hum Reprod. 2009; 24(9):2104-13. PMC: 2727402. DOI: 10.1093/humrep/dep198. View

12.

Choi B, Bosch E, Lannon B, Leveille M, Wong W, Leader A . Personalized prediction of first-cycle in vitro fertilization success. Fertil Steril. 2013; 99(7):1905-11. DOI: 10.1016/j.fertnstert.2013.02.016. View

13.

Altman D, Royston P . The cost of dichotomising continuous variables. BMJ. 2006; 332(7549):1080. PMC: 1458573. DOI: 10.1136/bmj.332.7549.1080. View

14.

Banerjee P, Choi B, Shahine L, Jun S, OLeary K, Lathi R . Deep phenotyping to predict live birth outcomes in in vitro fertilization. Proc Natl Acad Sci U S A. 2010; 107(31):13570-5. PMC: 2922227. DOI: 10.1073/pnas.1002296107. View

15.

Ravhon A, Aurell R, Lawrie H, Margara R, Winston R . The significance of delayed suppression using buserelin acetate and recombinant follicle-stimulating hormone in a long protocol in vitro fertilization program. Fertil Steril. 2000; 73(2):325-9. DOI: 10.1016/s0015-0282(99)00521-x. View

16.

Albuquerque L, Tso L, Saconato H, Albuquerque M, Macedo C . Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles. Cochrane Database Syst Rev. 2013; (1):CD002808. PMC: 7133778. DOI: 10.1002/14651858.CD002808.pub3. View

17.

Donders A, van der Heijden G, Stijnen T, Moons K . Review: a gentle introduction to imputation of missing values. J Clin Epidemiol. 2006; 59(10):1087-91. DOI: 10.1016/j.jclinepi.2006.01.014. View

18.

Lin H, Li Y, Li L, Zhang Q, Wang W, Chen X . Effect of delayed initiation of gonadotropin in luteal long protocol on in vitro fertilization. Gynecol Endocrinol. 2013; 29(9):846-50. DOI: 10.3109/09513590.2013.813475. View

19.

Greenland S, Finkle W . A critical look at methods for handling missing covariates in epidemiologic regression analyses. Am J Epidemiol. 1995; 142(12):1255-64. DOI: 10.1093/oxfordjournals.aje.a117592. View

20.

Shulman A, Ghetler Y, Beyth Y . The significance of an early (premature) rise of plasma progesterone in in vitro fertilization cycles induced by a "long protocol" of gonadotropin releasing hormone analogue and human menopausal gonadotropins. J Assist Reprod Genet. 1996; 13(3):207-11. DOI: 10.1007/BF02065937. View