First trimester pregnancy loss and live birth rate after ICSI in relation to age and ovarian response: outcome of 23.354 cycles.

Introduction: The number of live births per cycle and live births per embryo
transfer are commonly used outcome measures of in-vitro fertilisation treatment.
Limited data are available regarding the reproductive outcome per cycle
in relation to age and ovarian response. The aim of the current study is to quantify
the reproductive efficiency expressed as live birth rate and first trimester
loss per cycle according to ovarian age and ovarian response.
Methods: The current analysis is based on all consecutive ICSI data, collected
prospectively over a period of 18 years from 1992 until 2009, and stored in the
database of our academic reproductive medicine centre. Only ICSI cycles were
included in order to have the opportunity to examine mature oocytes. Cycles
with use of donated oocytes, surgically retrieved sperm or with use of preimplantation
genetic diagnosis or screening (PGD/PGS) were excluded. The
primary outcome was the live birth rate per cycle, starting at age 23 and ending
at age 43, and by ovarian response, categorised into three mutually exclusive
groups (1-5, 6-10, or 11 or more mature oocytes). Secondary outcomes
analysed in this study were the first trimester pregnancy loss as expressed by
preclinical abortion rate, miscarriage rate, and ectopic pregnancy rate. Multiple
regression modelling was used to quantify the independent impact of age and
ovarian response on each outcome of interest.
Results: The current analysis reports the outcome 23,354 ovarian stimulation
cycles performed consecutively in a single centre over an 18-year period from
1992 until 2009. The live birth rate was highly dependent on ovarian response:
compared to the referent ovarian response group with 11 or more mature
oocytes,the live birth rate was 4.3% lower in the response group with 6-10mature oocytes, and 16.4% lower in the response group with only 1-5 mature oocytes, as indicated by the regression coefficients for absolute rate differences adjusted for age of -4.3% (95% CI, -6.8% to -1.8; P = 0.001) and -16.4% (95%
CI, -18.9% to -13.9%; P <0.001), respectively.
The ectopic pregnancy rate did not correlated with the age of the patient
(P = 0.33). At any given age, the ectopic pregnancy rate was approximately
1.9%. Preclinical abortion and miscarriage rates, as well as overall first trimester
pregnancy loss rate, remained more or less constant until the age of 34, but
increased steadily from the age of 35 onwards. On average, preclinical abortion,
miscarriage, and overall first trimester pregnancy loss rates were 8.5%,
6.8%, and 16.9%, respectively, until the age of 37. In the 38-40 years group,
preclinical abortion, miscarriage, and overall first trimester pregnancy loss rates
increased by 5.3% (0.9 to 9.7%; P = 0.021), 9.8% (5.6 to 14.0%; P <0.001),
and 16.9% (12.7 to 21.0%; P <0.001), respectively. In the 41-43 years group,
these increases were even higher: 7.8% (3.4 to 12.2%; P = 0.002), 15.0% (10.7
to 19.2%; P <0.001), and 22.9% (18.7 to 27.1%; P <0.001), respectively.
Conclusions: These large prospectively collected ICSI outcome data enable the
assessment of treatment outcome expressed as live birth rate and first trimester
pregnancy loss per cycle. This study demonstrates the strong correlation between
ovarian response and the live birth rate after ICSI. The risk of first trimester
pregnancy loss significantly increases after the age of 38 years with an even
more pronounced increase after the age of 40. The risk of ectopic pregnancy is
independent of age, with an average of 1.9% per cycle.