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ORIGINAL RESEARCH |
From the Genetics and IVF Institute, Fairfax, Virginia.
Address reprint requests to: Michael S. Opsahl, MD Genetics and IVF Institute Fairfax, VA 22031 E-mail: mopsahl{at}givf.com
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Abstract |
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Methods: We reviewed clinical outcome data from sequential anonymous oocyte donation cycles using donors who underwent multiple IVF stimulations. Donors were grouped by the interval between cycles and the cycle number (rank). The primary outcome measure was delivery rate by individual donor per retrieval from the combined derivative fresh and frozen embryo transfers.
Results: Duration and amount of gonadotropin therapy and the fertilization rates did not correlate significantly with the interval between cycles or cycle rank. Cumulative delivered pregnancy rates for cycles 1–6 were 51.5%, 54.6%, 50.5%, 51.5%, 51.1%, and 57.6%, respectively. Delivered pregnancy rates did not vary by interval between cycles.
Conclusion: Young healthy presumed or proven fertile women can reliably donate oocytes for at least six cycles with the expectation of consistently high pregnancy rates.
In vitro fertilization (IVF) is an established successful treatment for infertile couples. Factors influencing pregnancy outcome include maternal age, embryo quality, number of embryos transferred, length of infertility, and infertility diagnosis.1,2 The influence of the number of previous IVF attempts on pregnancy outcome is less certain.3 Some studies of repeated IVF treatment among infertile women showed a significant decline in delivery rates with successive cycles.2,4,5 Others did not find such differences with repeated attempts.6–8
Donor oocyte IVF treatments are highly successful but are not as frequent as conventional IVF cycles.9,10 Most studies of donor oocyte IVF cycles focus on recipient outcomes rather than the cycle performance of individual donors.10,11 The influence of the number of completed IVF cycles by individual donors on pregnancy outcome in recipients to our knowledge has not been reported as it has for IVF cycles among infertile women.2,4,5
Most studies indicate a decline in pregnancy rates with repeated IVF attempts among infertile women, so we wanted to evaluate whether individual oocyte donors also had a decline in pregnancy rates with sequential donor IVF cycles. We studied pregnancy outcomes retrospectively in recipients as a function of cycle rank for each donor. We also evaluated whether the interval between donor cycles influenced pregnancy outcomes.
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Methods and Materials |
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Oocyte donors underwent standard IVF stimulation using short- or long-term GnRH agonist suppression followed by gonadotropin stimulation. Human chorionic gonadotropin was administered when the lead follicles were at least 18 mm in mean diameter. Outpatient ultrasound-guided oocyte retrieval was done with conscious sedation. The donors continued GnRH agonist suppression for 10 days postretrieval to minimize symptoms of ovarian hyperstimulation. Each cycle was ranked according to the order in which it occurred. A rest month was required between donation cycles such that oocyte retrievals were no more frequent than every other month.
Recipients were synchronized with their donors by withdrawal from hormone replacement therapy or by downregulation with oral contraceptives or GnRH agonist. After downregulation, each recipient received oral Estrace (Bristol-Myers Squibb Co., Princeton, NJ) twice daily. The dose was modified based on serum estrogen levels and endometrial thickness. Progesterone supplementation began on the day of donor oocyte retrieval. When pregnancy occurred, recipients continued hormone supplementation through 10 weeks’ gestation.
We defined an adequate endometrium as one exceeding 6 mm thickness with a triple-line appearance on ultrasonography. If the endometrial appearance was judged to be suboptimal for successful embryo transfer, embryos were ordinarily cryopreserved (unless the recipient insisted on an embryo transfer) and subsequently transferred in a separate hormone preparation cycle. Mock endometrial preparation cycles are rarely performed in our program unless women have already completed a mock cycle at another program site or requested a mock cycle for psychologic reassurance.
Embryo transfer occurred on the second or third day after oocyte retrieval. Study cycles were completed before initiation of a blastocyst embryo transfer program. Recipients determined the number of embryos transferred after physician counseling. Our routine recommendation was to transfer the three clinically best embryos unless embryo quality was extremely good or poor, then the number of transferred embryos was generally adjusted down or up, respectively, by one embryo. We have not placed an absolute limit on the number of embryos to be transferred because clinical circumstances sometimes dictate more or fewer embryos than usual. The embryos were transferred atraumatically under ultrasound guidance. Excess embryos were cryopreserved at the pronuclear stage until 1994 when most embryos were cryopreserved at the cleaved embryo stage.12
Clinical outcomes from fresh and derivative frozen embryo transfer cycles were combined to determine the outcome per retrieval. By combining fresh and frozen embryo transfers, we could determine the percentage of recipients who achieved at least one delivered pregnancy from the cumulative embryo transfers derived from each egg retrieval. We only included transfer cycles leading to the first delivered pregnancy per retrieval because some recipients achieved more than one delivered pregnancy per retrieval. For informational purposes only, the pregnancy rate per embryo transfer is listed in the Results.
We reviewed each donor cycle during monthly meetings. Our criteria for discontinuing donors from the program included at least two cycles that produced fewer than seven mature oocytes, poor fertilization resulting in four or fewer embryos, with at least two separate sperm donors regardless of the number of mature oocytes, or three cycles without a deliverable pregnancy (including frozen embryo transfer cycles). Poor oocyte production criteria for discontinuation were waived if recipient embryo transfers resulted in delivered pregnancies, in which case donors remained available for matching if the recipient couple was willing to accept the likelihood of fewer oocytes than in an average cycle. We temporarily withdrew donors from the matching pool when they cycled three times without a known viable gestation until they established a viable pregnancy from a frozen embryo transfer. Then the donor was reintroduced into the active donor pool with continued close monitoring of her performance. In summary, donors were discontinued from participation for low mature oocyte or embryo production but only when recipient couples failed to achieve delivered pregnancies.
Statistical analysis was computed with SPSS 10.01 (SPSS Inc., Chicago, IL) and SAS 6.12 (SAS, Cary, NC). Non-normal data distributions were transformed before performing parametric statistical analysis. These data are presented in nontransformed format for ease of presentation as the mean ± standard deviation. Statistical tests included analysis of variance, Cochran’s Q statistic for repeated measures, and exact 
2. Type I error (P) for this study was set at .05.
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Results |
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The 135 donors completed 511 cycles but only 503 cycles resulted in an embryo transfer. Five cycles produced no embryos and three cycles had all embryos cryopreserved without ever transferring the embryos. Intracytoplasmic sperm injection was performed in 40% of cycles for male factors and the frequency did not change by cycle rank. Intracytoplasmic sperm injection cycle clinical outcomes were similar to conventional cycles; therefore, the two cycle types were combined for statistical analysis.
The interval between donor cycles averaged 3.5 ± 4.8 months (median = 3.0) but ranged from 2 to 51 months. The interval between those cycles did not affect the mean number of days of stimulation, gonadotropin ampules used for stimulation, number of mature oocytes, or fertilization rate (Table 1
). Donor cycles with an interval greater than 12 months from the previous cycle produced significantly fewer embryos (P = .013, repeated measures analysis of variance). This observation must be considered tentative because it was based on very few cycles.
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). Mean number of mature oocytes and total embryos formed increased modestly but significantly with repeated cycles (P < .001, repeated measures analysis of variance). Donors involuntarily discontinued for poor stimulation were identified in early cycles, so donor selection might explain in part the apparent improvement in results with higher cycle rank. The incidence of severe ovarian hyperstimulation syndrome with ascites was approximately 2% in this study population and the incidence did not change with repeated cycles.
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shows that the interval between cycles did not significantly affect pregnancy outcome. Table 2 lists the pregnancy outcome data by cycle rank. The pregnancy outcomes were similar regardless of cycle rank. However, none of these analyses were based on adequate (at least 80%) statistical power. Eight donors classified as poor responders underwent 18 stimulated cycles and no embryo transfer occurred in three of those cycles. Two of those produced adequate numbers of mature oocytes but fertilization was poor with three separate recipient couples, yielding no frozen embryos and no viable pregnancies. The delivered pregnancy rate for the remaining 15 cycles was 13.3% (two of 15). Six donors were discontinued for not producing sufficient viable pregnancies. They were matched three to four cycles each for 21 total cycles. Only three (14.3%) delivered pregnancies resulted. Most cycles yielded a reasonable number of mature oocytes (12.4 ± 4.7) and embryos (5.9 ± 3.1), necessitating a longer trial before discontinuing them from the donor program to allow for the results of frozen embryo transfer cycles.
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Discussion |
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We observed consistently high recipient pregnancy rates from anonymous oocyte donors undergoing successive cycles. Donors maintained recipient delivery rates of over 50% through six donation cycles. The frequency of donation did not affect clinical outcomes. Donors exhibited a consistent response to gonadotropin stimulation even with closely spaced cycles (less than a 4-month interval). The increase in mature oocytes retrieved with increasing cycle rank likely represents a combination of improved ovarian stimulation from prior cycle experience, recipient selection bias for donors producing more oocytes, and exclusion of poor response donors from continued participation. We discontinued donors who consistently stimulated poorly or whose oocytes did not result in viable pregnancies. Two cycles were generally needed to classify a donor as a poor responder. Our observation of lower success rates in poor response donors confirms similar findings in infertile women.13,14
One limitation of this study was the lack of statistical power to rule out a type II error. To be confident that the lack of differences in delivered pregnancies across sequential cycles was not caused by inadequate sample size, we needed at least 523 individual donors to complete six cycles each or 3138 cycles to achieve 80% power. Most donors choose to discontinue their participation after three to four cycles, so that goal was very difficult even with a multicenter study. We believe the data from this experience are reassuring despite its statistical limitations.
This study, representing a large number of donor cycles, suggests that anonymous voluntary donors selected for health and fertility status can donate for at least six cycles without diminishing cycle characteristics or decreasing chances for a successful pregnancy. The frequency of donation had no effect on clinical outcome measures when the interval between cycles was shorter than 12 months.
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Footnotes |
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Received March 20, 2000. Received in revised form August 1, 2000. Accepted October 5, 2000.
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References |
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2. Templeton A, Morris JK, Parslow W. Factors that affect outcome of in-vitro fertilization treatment. Lancet 1996;348:1402–6.[Medline]
3. Zeyneloglu HB, Arici A, Olive DL. Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization–embryo transfer. Fertil Steril 1998;70:492–9.[Medline]
4. Tan SL, Royston P, Campbell S, Jacobs HS, Betts J, Mason B, et al. Cumulative conception and livebirth rates after in-vitro fertilization (comments). Lancet 1992;339:1390–4.[Medline]
5. Meldrum DR, Silverberg KM, Bustillo M, Stokes L. Success rate with repeated cycles of in vitro fertilization–embryo transfer. Fertil Steril 1998;69:1005–9.[Medline]
6. French National IVF Registry. Analysis of 1986 to 1990 data. FIVNAT (French In Vitro National). Fertil Steril 1993;59:587–95.[Medline]
7. Alsalili M, Yuzpe A, Tummon I, Parker J, Martin J, Daniel S, et al. Cumulative pregnancy rates and pregnancy outcome after in-vitro fertilization: >5000 cycles at one centre. Hum Reprod 1995;10: 470–4.
8. Alsalili M, Yuzpe AA, Tummon IS, Parker J, Martin JS, Nisker JA, et al. Confounding variables affecting in vitro fertilization success: A decade of experience. J Assist Reprod Genet 1995;12:88–92.[Medline]
9. Sauer MV, Paulson RJ, Ary BA, Lobo RA. Three hundred cycles of oocyte donation at the University of Southern California: Assessing the effect of age and infertility diagnosis on pregnancy and implantation rates. J Assist Reprod Genet 1994;11:92–6.[Medline]
10. Spandorfer SD, Moomjy M, Davis OK, Barmat LI, Cholst I, Rosenwaks Z. Oocyte donation: Does a previous attempt affect a subsequent attempt? Fertil Steril 1998;70:222–6.[Medline]
11. Paulson RJ, Hatch IE, Lobo RA, Sauer MV. Cumulative conception and live birth rates after oocyte donation: Implications regarding endometrial receptivity. Hum Reprod 1997;12:835–9.
12. Fugger EF, Bustillo M, Dorfmann AD, Schulman JD. Human preimplantation embryo cryopreservation: Selected aspects. Hum Reprod 1991;6:131–5.
13. Roest J, van Heusden AM, Mous H, Zeilmaker GH, Verhoeff A. The ovarian response as a predictor for successful in vitro fertilization treatment after the age of 40 years. Fertil Steril 1996;66:969–73.[Medline]
14. Dor J, Seidman DS, Ben Shlomo I, Levran D, Karasik A, Mashiach S. The prognostic importance of the number of oocytes retrieved and estradiol levels in poor and normal responders in in vitro fertilization (IVF) treatment. J Assist Reprod Genet 1992;9:228–32.[Medline]
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