Large blastocyst diameter, early blastulation, and low preovulatory serum progesterone are dominant predictors of clinical pregnancy in fresh autologous cycles.

Abstract

To identify dominant predictors of clinical pregnancy in IVF cycles.
Retrospective study.
Private fertility center.
The study included 580 fresh autologous IVF cycles with blastocyst transfer.
None.
Clinical pregnancy rate.
A set of 25 suspected predictors was used to develop predictive models of clinical pregnancy in a set of 361 blastocyst transfer cycles. Initial bivariate analysis identified 14 of these variables that were significant enough to be candidate variables for multiple logistic regression. Similar sets of significant variables were identified by using alternative approaches for model construction. The final model included blastocyst diameter, day of blastulation, and preovulatory serum P level as significant predictors of clinical pregnancy. Specifically, clinical pregnancy was predicted by preovulatory serum P of <1.0 ng/mL, blastulation on day 5, and large blastocyst diameter. Of these variables, blastocyst diameter was the most significant predictor of clinical pregnancy in the multivariate models. The final model was validated against a separate set of 219 subsequent blastocyst transfer cycles.
Pre-ovulatory serum P level, blastulation day, and embryo diameter are simultaneously predictive of clinical pregnancy, and their relationships with clinical pregnancy are consistent with an effect of embryo-endometrium synchrony.

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Chapter 8: Large blastocyst diameter, early blastulation, and low pre-ovulatory serum
progesterone are dominant predictors of clinical pregnancy in fresh autologous cycles
SOURCE (OR PART OF THE FOLLOWING SOURCE):
Type Dissertation
Title Optimal blastocyst transfer : the embryo and the endometrium
AuthorB.S. Shapiro
FacultyFaculty of Medicine
Year 2008
Pages 188
ISBN 978-90-71382-58-1
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Chapter 8

Large blastocyst diameter, early blastulation, and low pre-ovulatory serum
progesterone are dominant predictors of clinical pregnancy in fresh
autologous cycles

Bruce S. Shapiro, M.D., Said T. Daneshmand, M.D, Forest C. Garner, M.Sc.,
Martha Aguirre, Ph.D., Shyni Thomas, B.Sc.

Fertility and Sterility 2008;90:302-309.

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Abstract
Objective: To identify dominant predictors of clinical pregnancy in cycles of in
vitro fertilization (IVF).
Design: Retrospective study.
Setting: Private fertility center
Patient(s): The study included 580 fresh autologous IVF cycles with blastocyst
transfer.
Intervention(s): None.
Main Outcome Measures: Clinical pregnancy rate.
Results: A set of 25 suspected predictors was used to develop predictive models
of clinical pregnancy in a set of 361 blastocyst transfer cycles. Initial bivariate
analysis identified 14 of these variables that were significant enough to be
candidate variables for multiple logistic regression. Similar sets of significant
variables were identified with alternative approaches for model construction. The
final model included blastocyst diameter, day of blastulation and pre-ovulatory
serum progesterone level as significant predictors of clinical pregnancy.
Specifically, clinical pregnancy was predicted by pre-ovulatory serum
progesterone <1.0 ng/ml, blastulation on day 5, and large blastocyst diameter. Of
these variables, blastocyst diameter was the most significant predictor of clinical
pregnancy in the multivariate models. The final model was validated against a
separate set of 219 subsequent blastocyst transfer cycles.
Conclusions: Pre-ovulatory serum progesterone level, blastulation day, and
embryo diameter are simultaneously predictive of clinical pregnancy and their
relationships with clinical pregnancy are consistent with an effect of embryo-
endometrium synchrony.
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Introduction

The transfer of blastocysts instead of earlier stage embryos confers certain
advantages. Blastocyst transfer precludes the transfer of embryos that lack the
developmental potential to reach the blastocyst stage. Furthermore, compared to
earlier stages, blastocysts have a more complex and potentially informative
morphology that allows more elaborate and effective grading systems (1, 2, 3).

Some useful criteria for embryo grading are subjective or, if defined objectively,
are based on subjective assessment. For example, when deciding if the
proportion of volume that is occupied by the blastocele exceeds a stated criterion,
many would rely on visual judgement instead of measurement. A further limitation
of subjective embryo grading is the limited utility of nominal data (3). While
subjective criteria can be effective, the use of objectively measured criteria may
convey distinct advantages, including greater reproducibility. Some potentially
important objective and quantitative criteria include blastocyst diameter, size of the
inner cell mass, and the number of cells in the trophectoderm.

Blastocyst diameter, size of the inner cell mass, and the number of cells in the
trophectoderm can be readily and objectively measured. These measures, along
with day of blastulation, may be useful indicators of embryo developmental pace.
The authors and others have previously reported that the day of blastulation has a
significant correlation with implantation and pregnancy rates in cycles of fresh
blastocyst transfer (4, 5, 6). This effect is not observed in frozen blastocyst
transfer cycles (6, 7, 8, 9), suggesting the effect is related to embryo-endometrium
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synchrony. There are no prior reports relating blastocyst diameter to autologous
IVF cycle outcome in humans, although the transfer of fully expanded blastocysts
has been reported to yield a greater implantation rate than transfers of less
developed blastocysts (10, 11).

The likely impact of supraphysiological steroid levels on endometrial maturation
has been discussed previously (12). Elevated peri-ovulatory serum progesterone
(P) levels have been correlated with failure of fresh autologous IVF cycles (13,
14). This may reflect the effect of P on endometrial development. Studies of
oocyte donation cycles and thawed embryo transfers have noted a lack of
correlation, or even a positive correlation, between pre-ovulatory serum P in the
oocyte source cycle and pregnancy in recipients, suggesting that serum P does
not substantially affect oocyte quality (15, 16, 17, 18, 19).

The current study used many potentially significant independent variables to
construct models of clinical pregnancy as the dependent variable in multiple
logistic regression. Such multivariate analysis holds advantages over the usual
univariate or bivariate methods. For example, because multiple independent
variables are simultaneously considered, it may be determined if their effects are
redundant or if the additional variables bring additional predictive information to
the model.

146