Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, New York Presbyterian Medical Center, College of Physicians and Surgeons, Columbia University, New York, USA
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Abstract |
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Key words: age/gravidity/in-vitro fertilization/oocyte donor/parity
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Introduction |
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We chose to address these questions using a large database to ascertain which variables (donor age, gravidity, parity, or the number of oocytes retrieved), if any, are important predictors of outcome. The database is unique since all donors were directed to individual recipients, and not shared. In addition, since only paid donors were utilized, all eggs were used for individual cycles, and the data were not biased by embryo selection or other confounding variables present when infertile women are used as donors.
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Materials and methods |
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Statistical analysis was performed using the SAS package (SAS Institute, Cary, NC, USA). The statistical significance of association was tested by Student's t-test for continuous data, and by the 2 test for nominal data. The strength of association was assessed by odds ratios. The multivariate logistical regression model was applied to calculate the odds ratios for donor age and pregnancy, with adjustment for gravidity, parity, and oocyte number at retrieval. P < 0.05 was considered to be statistically significant.
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Results |
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The donor's previous gravidity and parity were negatively associated with pregnancy. After correcting for donor age, however, prior fertility was not a significant predictor of cycle outcome (Table I). Cycles resulting in pregnancies had a significantly higher number of retrieved oocytes. Once again, after correcting for donor age, the significance of oocyte number at retrieval on pregnancy disappeared (Table I
).
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Discussion |
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Previous studies have shown a positive effect of younger donor age on IVF outcome. Balmaceda et al. evaluated 258 donor cycles and found a significant decline in the pregnancy rate at ages of >35 years, although the statistical significance disappeared after logistic regression analysis (Balmaceda et al., 1994). Rotsztejn and Asch studied 108 donor cycles; they divided the donors into their 20s and 30s and found a significantly higher clinical pregnancy rate in the younger group (Rotsztejn and Asch, 1991
). Faber et al. appraised 568 donor cycles and noted a significant decline in both clinical and delivered pregnancy rate in donors aged
33 years (26.6 and 22.1% compared with 43.5 and 35.1% respectively), and suggested that donors aged >32 years could be excluded from donor programmes (Faber et al., 1997
).
Several studies have not found a significant effect of donor age on IVF outcome. Donor age was positively associated with pregnancy rate in 100 cycles (Abdalla et al., 1990). In a continuation of their series, these authors (Abdalla et al., 1993
) evaluated 371 donor cycles and found no effect of donor age on clinical pregnancy rate up to and including age 39, although an increase in miscarriage was noted in cycles employing older donors. While donor age was equivalent in both successful and unsuccessful cycles, no evaluation of separate age categories was performed. Similarly, this study is a continuation of series (Wong et al., 1996
; Stolwijk et al., 1997
) that found different results based upon an expanding database. Wong et al. divided 458 donor cycles from 19881995 into two groups: one in their 20s and the other in their 30s (Wong et al., 1996
). The younger group had more oocytes per retrieval, but no benefit was noted in either clinical or delivered pregnancy rate. Even when donor age was split into 5 year categories, no evidence of an age effect was present. They did not control for donor gravidity, parity, or number of oocytes. The second study (Stolwijk et al., 1997
) was limited to include only the first recipient cycle, but reached the same conclusions. They evaluated 294 donor cycles from 19911995 and also found a decrease in oocytes retrieved with advancing donor age. After sorting the donors by 5 year intervals they found no effect of donor age on pregnancy rate. The present study used an expanded data set of 621 donor cycles from 19911997. As mentioned earlier, we excluded cycles for which data was missing on any of the variables studied, leaving 445 of 621 cycles for evaluation. The series reported earlier had a bell-shaped curve for donor age, while the current study has a more even age distribution, enabling a more accurate interpretation at the age extremes. Furthermore, we divided the cycles into seven groups by 3 year intervals, again increasing the statistical accuracy. We found that the younger donors had a significant benefit on pregnancy rate, even after controlling for prior donor fertility, number of oocytes, and the site of the cycle.
The effect of donor gravidity and parity in this study suggests that prior fertility is adversely associated with pregnancy outcome (Table I). Corrected for donor age, however, the effect of previous donor fertility became insignificant.
Faber et al. evaluated 185 cycles for the effect of donor gravidity and came to the same conclusion (Faber et al., 1997). In contrast, another study (Darder et al., 1996
) included only 64 cycles and found that prior donor gravidity was positively associated with pregnancy outcome. This result may be an artefact of small sample size. In addition, Rotsztejn et al. evaluated donor parity in 83 regular donor cycles and concluded that it was an insignificant predictor of outcome (Rotsztejn et al., 1992
). The first study by Abdalla et al. reported donor parity in 100 cycles and found that prior donor parity and younger donor age were both positively associated with pregnancy rate in that sample (Abdalla et al., 1990
). However, when they increased their sample size by nearly four times in a later study, their conclusions regarding donor age were reversed (Abdalla et al., 1993
).
We did not control for recipient age, but most large series evaluating recipient age have demonstrated no effect (Rotsztejn and Asch, 1991; Sauer et al., 1992
; Abdalla et al., 1993
; Balmaceda et al., 1994
; Navot et al., 1994
; Check et al., 1995
; Legro et al., 1995
; Remohí et al., 1997
; Stolwijk et al., 1997
). A smaller number of papers suggest an adverse effect of advanced recipient age (Yaron et al., 1993
; Flamigni et al., 1993
; Cano et al., 1995
; Borini et al., 1996
; Levran et al., 1996
); some of these used subfertile women (women undergoing IVF themselves who donated their excess oocytes) as donors (Yaron et al., 1993
; Levran et al., 1996
). Recipient age most likely did not confound our results and was certainly less significant in proportion to the effect of the ageing oocyte donor. Similarly, we did not control for paternal age. Other authors (Gallardo et al., 1996
) found no significance of paternal age on outcome of oocyte donation through to age 64 years.
In summary, we suggest younger donors provide higher chances for pregnancy in recipients but we do not recommend a firm upper-age limit. Rather, we believe a recipient couple should be informed of donor age as one characteristic among others, such as physical appearance, to consider in choosing an appropriate donor. Although a 35 year old donor is not as fecund as a 21 year old, her physical traits or ethnic background may nonetheless make her a more desirable choice for some. We do not consider the drop-off in pregnancy rates, ~2530%, so overwhelmingly significant as to constitute an absolute contraindication to the use of oocytes from older donors. Prior fertility, on the other hand, is not a significant donor attribute.
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Notes |
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* Presented at the 54th Annual Meeting of the American Society of Reproductive Medicine, San Francisco, CA, USA, October 49, 1998
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References |
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Submitted on February 2, 1999; accepted on June 16, 1999.