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Shared oocyte donation: society’s benefits
FERTILITY AND STERILITY威 VOL. 73, NO. 6, JUNE 2000 Copyright ©2000 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A.
Shared oocyte donation: society’s benefits Maureen Moomjy, M.D.,a Robin Mangieri, M.A.,b Fernando Beltramone, M.D.,c Ina Cholst, M.D.,b Lucinda Veeck, M.L.T.,b and Zev Rosenwaks, M.D.b New York Presbyterian Hospital, New York, New York; Center for Reproductive Medicine and Infertility, Weill Medical College, Cornell University, New York, New York; and CIGOR, Cordoba, Argentina
Received September 28, 1999; revised and accepted February 9, 2000. Reprint requests: Maureen Moomjy, M.D., 860 Fifth Avenue, New York, New York 10021 (FAX: 212-6399413; E-mail: mmoomjy @aol.com). a Department of Obstetrics and Gynecology, New York Presbyterian Hospital. b Center for Reproductive Medicine and Infertility, Weill Medical College, Cornell University, New York, New York. c CIGOR, Cordoba, Argentina. 0015-0282/00/$20.00 PII S0015-0282(00)00539-2
Objective: To assess the efficacy of oocyte donation when a cohort of oocytes is shared between two phenotypically matched recipients. Design: A retrospective analysis of a program using shared anonymous oocyte donation. Setting: Academic infertility center. Patient(s): Recipient women with partial or complete ovarian failure; oocyte donors who have been properly screened. Intervention(s): Each oocyte donor was phenotypically matched with two potential recipients. The cohort of donated oocytes were divided between these two recipients if eight or more mature oocytes were obtained at retrieval. Recipients underwent hormone replacement therapy consisting of down-regulation with a GnRH agonist, transdermal estradiol, and intramuscular progesterone in a dose determined by a previous preparatory cycle. Main Outcome Measure(s): Pregnancy and delivery rates for all transfers originating from a cohort of oocytes obtained by retrieval of a single donor; pregnancy and delivery rates per recipient; rate of conversion of a shared donation cycle to a single recipient. Result(s): A total of 249 donor cycles permitted 241 retrievals. Each recipient received 8.3 ⫾ 3.5 oocytes per donation. There were 424 fresh ETs and 48 frozen ETs performed. For fresh ETs, clinical pregnancy and ongoing or delivery rates per recipient were 56.8% and 49.7%, respectively. For frozen ETs, these rates were 50% and 39.5%. Implantation rates were 31.8% and 26.1% for fresh and frozen ET, respectively. When analyzed per donor retrieval, clinical pregnancy and ongoing or delivery rates were 109.5% and 95.4%. These high pregnancy rates per donor reflect the numerous fresh and frozen ETs that can result from one donor’s retrieval. Conversion of a donation cycle from two recipients to one recipient occurred for 26 of 241 cycles (10.8%). Conclusion(s): Shared anonymous oocyte donation provides a very high pregnancy rate per donor retrieval that is not achievable with unshared donation. In addition, there is a diminished risk exposure of donors per total completed recipient transfers. We support shared oocyte donation as the most efficient use of the precious resource of human oocytes. (Fertil Steril威 2000;73:1165–9. ©2000 by American Society for Reproductive Medicine.) Key Words: Oocyte donation, shared donor, cost-effectiveness, donor, recipient
For patients with ovarian failure, IVF is not a medical option. Nonetheless, these patients have a good chance of achieving pregnancy with oocyte donation. The known time, effort, commitment, discomfort, and minor risks derived from ovarian stimulation and oocyte retrieval continue to limit donor availability (1–3). Donor recruitment is a difficult endeavor, taking into account that a considerable number of potential donors may have a positive finding on medical, genetic, or psychological testing that prohibits donation. Providing oocyte dona-
tion to two recipients from a single cohort of eggs obtained from a single donor has the theoretic advantage of permitting a greater amount of fresh ETs. Historically, shared donation involved IVF patients willing to donate half of their oocytes to a recipient, often for reduction of treatment costs (1, 2, 4). Since 1993, IVF patients have not participated in shared oocyte donation at our center because embryo cryopreservation provides them a reasonable opportunity for another pregnancy attempt. Additionally, possible compromised oocyte quality and potential for psychological 1165
distress, women with past or current infertility are no longer permitted to donate in our center. Published studies (5, 6) on shared donor oocyte donation have focused on implantation and pregnancy rates for recipients of different ages. However, a comparison of outcome measures according to donor stimulation vs. recipient transfer has not yet been reported. Our objective was to evaluate the benefits of a program consisting of shared anonymous oocyte donation, in success rates per recipient transfer and per donor retrieval. Specifically, the goal was to quantify pregnancy, delivery, and implantation rates according to donor stimulation and retrieval and to assess these same outcome measures according to recipient transfer. In addition, we analyzed donor cycles that were converted to single recipients for the same outcome measures.
MATERIALS AND METHODS A retrospective analysis was performed for all donors and recipients participating in anonymous shared donor oocyte donation from August 1, 1990, to July 1, 1999, at the Center for Reproductive Medicine and Infertility, The New York Presbyterian-Weill Medical College of Cornell University.
Donors All anonymous donors were thoroughly screened and tested by a physician, geneticist, and psychologist. The goals of evaluations were directed toward protecting the health of the donor, the recipient, and the potential offspring, as previously reported (7). Only those patients completing testing and consultation with normal results were enrolled as donors. Age range of anonymous donors was 21 to and including 34 years. Because the center strictly limits oocyte retrieval and donation to a total of three cycles per donor, those donors having completed and passed all screening testing may have donated up to three times in a lifetime. Each oocyte donor was matched to two potential recipients, based on phenotypic characteristics. Shared matching of one donor never included more than two recipients. Criteria for conversion from shared oocyte donation to unshared oocyte donation included lack of sufficient mature oocytes for two recipients or cancellation by a recipient for medical or personal reasons. Permission for a planned unshared donation cycle at the time of the match occurred when there was lack of another phenotypically appropriate recipient couple or when there was history of severely compromised fertilization with intracytoplasmic sperm injection (ICSI) in a previous IVF or oocyte donation cycle. There were 26 planned unshared anonymous donation cycles during this time not included in the analysis. The screening and consenting process and the clinical management of donors and recipients has been monitored under Institutional Re1166 Moomjy et al.
Shared oocyte donation: society’s benefits
view Board protocol 0695-96 of the Committee for Human Rights in Research, The New York Hospital—Cornell University Medical College. Donor stimulation consisted of oral contraceptive pills in a previous cycle, with overlapping long leuprolide acetate protocol starting on pill day 14. Gonadotropins (FSH and/or MG) were generally given starting at three ampules per day for the first 2 days, with adjustments of the dose according to the ovarian response, measured by ultrasound and estradiol levels. Donors ⬎30 years of age were started on three or four ampules per day on the basis of day 3 FSH and ultrasound assessment of antral follicles during natural cycles. Criteria for hCG administration (10,000 or 5,000 IU) was at least two follicles of 17 mm with a normal rising estradiol.
Recipients Medical indications to be considered as a recipient of oocyte donation included premature or physiological ovarian failure, incipient ovarian failure precluding an IVF attempt, poor embryo or oocyte quality in repeated IVF cycles, and inheritable disease of which the mother was a carrier. Most recipients were referred for oocyte donation because of incipient ovarian failure or poor IVF history. Preparation of recipients included confirmation of a normal uterine cavity by means of hysterosalpingogram or saline infusion ultrasound. In addition, all recipients completed a preparatory cycle to measure endometrial response to exogenous estradiol and progesterone. Assessment of preparatory cycles included serum steroid levels, measurement of endometrial thickness with endovaginal ultrasound, and an endometrial biopsy for histologic review. Semen analyses were performed on recipients’ husbands and, when indicated, antisperm antibody testing was included. Couples were given the option of undergoing ICSI when there was clinical evidence of a possible fertilization failure, and ICSI only was performed on the day of retrieval. No ICSI was performed as a rescue procedure after retrieval day. For hormonal synchronization, the recipients underwent down-regulation with GnRH agonist (leuprolide acetate, 1 mg s.c. per day from midluteal phase) to achieve pituitary suppression if there was evidence of spontaneous ovarian function. For estrogen supplementation, we used increasing transdermal estradiol patches (0.1 mg) to simulate natural cycle levels, followed by progesterone in oil i.m. 25 mg on the day before oocyte donation and augmented to 50 mg i.m. daily for the subsequent days (7). Measurement of estradiol and progesterone levels and endometrial thickness assessed by ultrasonography was used in a similar way as in the preparatory cycle. For cryopreservation, only those recipients who received a frozen ET after a previous fresh ET were included in the study. The recipients who just received frozen ET because of synchronization or medical problems were excluded from the population studied. Vol. 73, No. 6, June 2000
TABLE 1 Patient and cycle data. Patient data
Results
Mean (⫾SD) recipient age in y Mean (⫾SD) donor age in y No. of donor cycles initiated No. of donor cancellations/no. of initiated cycles No. of donors completing oocyte retrievals No. of unshared donation cycles/no. of retrievals Mean (⫾SD) no. of oocytes received per recipient No. of recipients with no fertilized oocytes Total recipient cancellation ratea (cancelled/initiated)
40.9 ⫾ 4.4 28.1 ⫾ 3.7 249 8/249 (3.2%) 241 26/241 (10.8%) 8.3 ⫾ 3.5 13 39/511 (7.6%)
a
Total number of recipients with no transfer due to cycle conversion or no fertilization. Moomjy. Shared oocyte donation. Fertil Steril 2000.
Definition of Variables Pregnancy rate per recipient reflects the sum of all pregnancies with at least one fetal heartbeat divided by the total number of completed transfers. This measure is the potential for pregnancy that a recipient would anticipate. Pregnancy rate per donor retrieval reflects the sum of all pregnancies with at least one fetal heartbeat divided by the total number of completed donor retrievals. This measure is the potential for pregnancy that the center can anticipate per donor stimulation and completed retrieval. Ongoing pregnancy and delivery rate includes all completed deliveries and pregnancies in the second or third trimester divided by recipient transfer or donor retrieval as indicated. A biochemical pregnancy, considered as rise and fall of -hCG levels before 7 weeks’ gestation, was recorded as negative for pregnancy. Implantation rate is the sum of all fetal heartbeats divided by the sum of all embryos transferred. A miscarriage is the loss of the fetal heartbeat of a clinical pregnancy.
RESULTS The donors’ mean (⫾SD) age was 28.1 ⫾ 3.7 years; the recipients’ mean (⫾SD) age was 40.9 ⫾ 4.4 years. A total of 249 shared anonymous donor cycles were initiated, of which 241 retrievals occurred. The cancellation rate for donors, generally because of high response to ovarian stimulation, was 3.2% (8 of 249 patients). The need to convert from shared to unshared donation generally for low response with the cancellation of one recipient occurred in 10.8% (26 of 241 donors) of the recipient cycles. For 13 recipients, no fertilization occurred. The recipient cancellation rate for both cycle conversion to unshared donation and no fertilization combined was 39 of 511 cycles (7.6%). Each recipient received a mean (⫾SD) of 8.3 ⫾ 3.5 oocytes per donation cycle. Data are depicted in Table 1.
Recipient Outcome Measures In this study, 241 anonymous oocyte donation retrievals resulted in ET for 472 recipients. Fresh transfers were perFERTILITY & STERILITY威
formed in 424 recipients, and frozen ETs in 48 recipients (Table 2). Given recent implantation data for this center, recipient couples have been advised to accept two or three embryos at transfer. Before 1994, some transfers involved four embryos, given the lower implantation rate during that time. Clinical pregnancy rate per recipient fresh ET was 56.8%, with ongoing pregnancy and delivery rate of 49.7%. For recipients with frozen ET, these rates were 50% and 39.5%, respectively. The implantation rates were 31.8% and 26.1%, for fresh ET and frozen ET, respectively. The miscarriage rate was 12.4% for fresh ET and 20.8% for frozen ET. There were four ectopic pregnancies, which were considered negative for pregnancy in these statistics. Outcome data are depicted in Table 3.
Outcomes As Measured Per Donor Retrieval When calculated according to a single cohort of oocytes retrieved from a single donor, the donor cumulative pregnancy rate for all fresh and frozen ETs was 109.5%, and the ongoing pregnancy and delivery rate was 95.4%. This per donor pregnancy rate of ⬎100% is the result of shared donation that yielded an average of two recipient transfers per single donor retrieval. For fresh ET results alone, clinical pregnancy rate and ongoing pregnancy and delivery rate calculated per cohort of oocytes of a single donor retrieval were 100% and 87.5%, respectively. Conversion of a shared donation cycle to an unshared donation cycle occurred in 26 of 241 donor cycles (10.8%) (Table 1), because of low egg yield (19 recipients), for medical or personal reasons (5 recipients), and because of inadequate synchronization (2 recipients).
DISCUSSION The number of women with partial or complete ovarian failure requesting oocyte donation is far greater than the availability of women willing to participate in oocyte donation. Because of the rigorous testing for potential genetic or infectious diseases and because of the extraordinary commitment required, our experience has been that ⬍50% of the
TABLE 2 Transfer data per donor retrieval resulting from shared oocyte donation.
Fresh ET Frozen ET Fresh and frozen ET combined
Total number of recipient transfers
Total number of donors retrieved
424 48
241
1.75 0.20
472
241
1.95
Mean transfers per donor
Moomjy. Shared oocyte donation. Fertil Steril 2000.
1167
mize donor risks and medication exposure weighs in favor of continuing with shared oocyte donation.
TABLE 3 Outcome data for recipients of shared donor oocyte donation.
Clinical pregnancies Fresh ET Frozen ET Fresh ET ⫹ frozen ET Ongoing pregnancies and deliveries Fresh ET Frozen ET Fresh ET ⫹ frozen ET Implantation rate Fresh ET Frozen ET Fresh ET ⫹ frozen ET
No. of outcomes/total no. of ETs (%)
No. of outcomes/no. of retrievals (%)
241/424 (56.8) 24/48 (50.0) 264/472 (55.9)
241/241 (100) 24/40 (60.0) 264/241 (109.5)
211/424 (49.7) 19/48 (39.5) 230/472 (48.7)
211/241 (87.5) 19/40 (47.5) 230/241 (95.4)
430/1,350 (31.8) 36/138 (26.1) 466/1,488 (31.3)
Moomjy. Shared oocyte donation. Fertil Steril 2000.
donors starting the process of screening actually are approved to proceed to stimulation and retrieval. Because of this imbalance between need for donation and availability of donors, recipients often wait longer than expected until a matched donor is available. Shared oocyte donation has emerged as a more efficient use of this precious resource of human oocytes. From our series results, 90% of the time there was an adequate number of healthy mature oocytes available at the time of donation for two recipients. Because the mean number of oocytes received in shared donation is 8.3, it is anticipated that the recipient will receive the recommended fresh ET of two or three embryos to have a 57% chance of a clinical pregnancy. This form of oocyte disposition permits less exposure of donors per families completed. It has been our experience that almost all oocyte retrievals in anonymous donation cycles will result in a clinical pregnancy, taking into account both fresh and frozen recipient ET combined. Nevertheless, shared ovum donation does result in an overall reduction of embryos available for cryopreservation. It is recognized that many couples consider this a disadvantage. Ultimately, at our center, 48.2% of the pregnancies are multiple gestations and probably completed families. Although 51.8% of the pregnancies are singleton gestations, about one third to one half of our recipients already have one child at home. For 43% of the recipients who are not pregnant on a given fresh ET and for the 13% who happen to miscarry, an opportunity for a frozen ET in an expeditious fashion is highly desirable. To date, 30.3% of shared anonymous oocyte donation cycles have also provided for frozen embryos at our center. We believe that the responsibility to optimize donor management and to mini1168 Moomjy et al.
Shared oocyte donation: society’s benefits
Another advantage of this approach is that having two potential recipients per donor permits completion of ovarian stimulation and retrieval in the event that one recipient cancels her cycle for medical or personal reasons. There are concerns about increasing the possibility of inadvertent consanguinity brought about by the use of shared oocyte donation. Because some parents may choose not to disclose to their children their genetic origins when oocyte donation is used, it is remotely possible to have unknown consanguinity between individuals genetically related to the same oocyte donor. The risk of potential unknown consanguinity is not absent in unshared oocyte donation because donors may have their own children. This raises responsibility issues for the programs, to limit the number of donor attempts, for donor safety and to avoid future couples of unknowing genetic half-siblings. National guidelines by the American Society for Reproductive Medicine for prudent limitation of retrievals and pregnancies per donor are currently being debated. In addition, couples should be counseled about the rare possibility of unknown consanguinity, a risk that can be lessened with disclosure. There is still no consensus concerning the association between ovarian stimulation and epithelial ovarian carcinoma (8 –12), but it is clear that this theoretical risk is a concern. By means of shared oocyte donation, we have been able to decrease the population of donors exposed to ovarian stimulation for a given population of recipients. Alternatively, a conservative limit on total donation cycles per donor can be set to similarly reduce exposure to ovarian stimulation. This is an issue of importance when one must decide on risk exposures. Cost reduction with this form of treatment is obvious. By comparing costs between our program of shared oocyte donation and other oocyte donation programs in the region, we found that costs for shared donation are 39% lower than unshared donation. For anonymous oocyte donation, sharing of oocytes between two phenotypically matched recipients provides a good opportunity for the recipient to experience pregnancy, while keeping medical risks and discomforts to an absolute minimum for the donor group. Precious human oocytes are well utilized in shared oocyte donation. References 1. Ahuja KK, Mostyn BJ, Simons EG. Egg sharing and egg donation: attitudes of British egg donors and recipients. Hum Reprod 1997;12: 2845–52. 2. Ahuja KK, Simons EG, Fiamanya W, Dalton M, Armar NA, Kirkpatrick P, et al. Egg-sharing in assisted conception: ethical and practical considerations. Hum Reprod 1996;11:1126 –31. 3. Englert Y, Govaerts I. Oocyte donation: particular technical and ethical aspects. Hum Reprod 1998;13(Supp 2):90 –7. 4. Peskin BD, Austin C, Lisbona H, Goldfarb JM. Cost analysis of shared oocyte in vitro fertilization. Obstet Gynecol 1996;88:428 –30.
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5. Abdalla HI, Wren ME, Thomas A, Korea L. Age of the uterus does not affect pregnancy or implantation rates; a study of egg donation in women of different ages sharing oocytes from the same donor. Hum Reprod 1997;12:827–9. 6. Borini A, Bianchi L, Violini F, Maccolini A, Cattoli M, Flamigni C. Oocyte donation program: pregnancy and implantation rates in women of different ages sharing oocytes from single donor. Fertil Steril 1996; 65:94 –7. 7. Rosenwaks Z. Donor eggs: their application in modern reproductive technologies. Fertil Steril 1987;47:895–909. 8. Rossing MA, Daling JR, Weiss NS, Moore DE, Self SG. Ovarian tumors in a cohort of infertile women. N Engl J Med 1994;331:771– 6.
FERTILITY & STERILITY威
9. Shushan A, Paltiel O, Iscovich J, Elchalal U, Peretz T, Schenker JG. Human menopausal gonadotropin and the risk of epithelial ovarian cancer. Fertil Steril 1996;65:13– 8. 10. Mosgaard BJ, Lidegaard O, Kruger Kjaer S, Schou G, Nyboe Andersen A. Infertility, fertility drugs, and invasive ovarian cancer: a case-control study. Fertil Steril 1997;67:1005–11. 11. Parazzini F, Negri E, La Vecchia C, Moroni S, Franceschi S, Crosignani PG. Treatment for infertility and risk of invasive epithelial ovarian cancer. Hum Reprod 1997;12:2159 – 61. 12. Mosgaard BJ, Lidegaard O, Nyboe Andersen A. The impact of parity, infertility and treatment with fertility drugs on the risk of ovarian cancer. Acta Obstet Gynecol Scand 1997;76:89 –95.
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Shared oocyte donation: society’s benefits Maureen Moomjy, M.D.,a Robin Mangieri, M.A.,b Fernando Beltramone, M.D.,c Ina Cholst, M.D.,b Lucinda Veeck, M.L.T.,b and Zev Rosenwaks, M.D.b New York Presbyterian Hospital, New York, New York; Center for Reproductive Medicine and Infertility, Weill Medical College, Cornell University, New York, New York; and CIGOR, Cordoba, Argentina
Received September 28, 1999; revised and accepted February 9, 2000. Reprint requests: Maureen Moomjy, M.D., 860 Fifth Avenue, New York, New York 10021 (FAX: 212-6399413; E-mail: mmoomjy @aol.com). a Department of Obstetrics and Gynecology, New York Presbyterian Hospital. b Center for Reproductive Medicine and Infertility, Weill Medical College, Cornell University, New York, New York. c CIGOR, Cordoba, Argentina. 0015-0282/00/$20.00 PII S0015-0282(00)00539-2
Objective: To assess the efficacy of oocyte donation when a cohort of oocytes is shared between two phenotypically matched recipients. Design: A retrospective analysis of a program using shared anonymous oocyte donation. Setting: Academic infertility center. Patient(s): Recipient women with partial or complete ovarian failure; oocyte donors who have been properly screened. Intervention(s): Each oocyte donor was phenotypically matched with two potential recipients. The cohort of donated oocytes were divided between these two recipients if eight or more mature oocytes were obtained at retrieval. Recipients underwent hormone replacement therapy consisting of down-regulation with a GnRH agonist, transdermal estradiol, and intramuscular progesterone in a dose determined by a previous preparatory cycle. Main Outcome Measure(s): Pregnancy and delivery rates for all transfers originating from a cohort of oocytes obtained by retrieval of a single donor; pregnancy and delivery rates per recipient; rate of conversion of a shared donation cycle to a single recipient. Result(s): A total of 249 donor cycles permitted 241 retrievals. Each recipient received 8.3 ⫾ 3.5 oocytes per donation. There were 424 fresh ETs and 48 frozen ETs performed. For fresh ETs, clinical pregnancy and ongoing or delivery rates per recipient were 56.8% and 49.7%, respectively. For frozen ETs, these rates were 50% and 39.5%. Implantation rates were 31.8% and 26.1% for fresh and frozen ET, respectively. When analyzed per donor retrieval, clinical pregnancy and ongoing or delivery rates were 109.5% and 95.4%. These high pregnancy rates per donor reflect the numerous fresh and frozen ETs that can result from one donor’s retrieval. Conversion of a donation cycle from two recipients to one recipient occurred for 26 of 241 cycles (10.8%). Conclusion(s): Shared anonymous oocyte donation provides a very high pregnancy rate per donor retrieval that is not achievable with unshared donation. In addition, there is a diminished risk exposure of donors per total completed recipient transfers. We support shared oocyte donation as the most efficient use of the precious resource of human oocytes. (Fertil Steril威 2000;73:1165–9. ©2000 by American Society for Reproductive Medicine.) Key Words: Oocyte donation, shared donor, cost-effectiveness, donor, recipient
For patients with ovarian failure, IVF is not a medical option. Nonetheless, these patients have a good chance of achieving pregnancy with oocyte donation. The known time, effort, commitment, discomfort, and minor risks derived from ovarian stimulation and oocyte retrieval continue to limit donor availability (1–3). Donor recruitment is a difficult endeavor, taking into account that a considerable number of potential donors may have a positive finding on medical, genetic, or psychological testing that prohibits donation. Providing oocyte dona-
tion to two recipients from a single cohort of eggs obtained from a single donor has the theoretic advantage of permitting a greater amount of fresh ETs. Historically, shared donation involved IVF patients willing to donate half of their oocytes to a recipient, often for reduction of treatment costs (1, 2, 4). Since 1993, IVF patients have not participated in shared oocyte donation at our center because embryo cryopreservation provides them a reasonable opportunity for another pregnancy attempt. Additionally, possible compromised oocyte quality and potential for psychological 1165
distress, women with past or current infertility are no longer permitted to donate in our center. Published studies (5, 6) on shared donor oocyte donation have focused on implantation and pregnancy rates for recipients of different ages. However, a comparison of outcome measures according to donor stimulation vs. recipient transfer has not yet been reported. Our objective was to evaluate the benefits of a program consisting of shared anonymous oocyte donation, in success rates per recipient transfer and per donor retrieval. Specifically, the goal was to quantify pregnancy, delivery, and implantation rates according to donor stimulation and retrieval and to assess these same outcome measures according to recipient transfer. In addition, we analyzed donor cycles that were converted to single recipients for the same outcome measures.
MATERIALS AND METHODS A retrospective analysis was performed for all donors and recipients participating in anonymous shared donor oocyte donation from August 1, 1990, to July 1, 1999, at the Center for Reproductive Medicine and Infertility, The New York Presbyterian-Weill Medical College of Cornell University.
Donors All anonymous donors were thoroughly screened and tested by a physician, geneticist, and psychologist. The goals of evaluations were directed toward protecting the health of the donor, the recipient, and the potential offspring, as previously reported (7). Only those patients completing testing and consultation with normal results were enrolled as donors. Age range of anonymous donors was 21 to and including 34 years. Because the center strictly limits oocyte retrieval and donation to a total of three cycles per donor, those donors having completed and passed all screening testing may have donated up to three times in a lifetime. Each oocyte donor was matched to two potential recipients, based on phenotypic characteristics. Shared matching of one donor never included more than two recipients. Criteria for conversion from shared oocyte donation to unshared oocyte donation included lack of sufficient mature oocytes for two recipients or cancellation by a recipient for medical or personal reasons. Permission for a planned unshared donation cycle at the time of the match occurred when there was lack of another phenotypically appropriate recipient couple or when there was history of severely compromised fertilization with intracytoplasmic sperm injection (ICSI) in a previous IVF or oocyte donation cycle. There were 26 planned unshared anonymous donation cycles during this time not included in the analysis. The screening and consenting process and the clinical management of donors and recipients has been monitored under Institutional Re1166 Moomjy et al.
Shared oocyte donation: society’s benefits
view Board protocol 0695-96 of the Committee for Human Rights in Research, The New York Hospital—Cornell University Medical College. Donor stimulation consisted of oral contraceptive pills in a previous cycle, with overlapping long leuprolide acetate protocol starting on pill day 14. Gonadotropins (FSH and/or MG) were generally given starting at three ampules per day for the first 2 days, with adjustments of the dose according to the ovarian response, measured by ultrasound and estradiol levels. Donors ⬎30 years of age were started on three or four ampules per day on the basis of day 3 FSH and ultrasound assessment of antral follicles during natural cycles. Criteria for hCG administration (10,000 or 5,000 IU) was at least two follicles of 17 mm with a normal rising estradiol.
Recipients Medical indications to be considered as a recipient of oocyte donation included premature or physiological ovarian failure, incipient ovarian failure precluding an IVF attempt, poor embryo or oocyte quality in repeated IVF cycles, and inheritable disease of which the mother was a carrier. Most recipients were referred for oocyte donation because of incipient ovarian failure or poor IVF history. Preparation of recipients included confirmation of a normal uterine cavity by means of hysterosalpingogram or saline infusion ultrasound. In addition, all recipients completed a preparatory cycle to measure endometrial response to exogenous estradiol and progesterone. Assessment of preparatory cycles included serum steroid levels, measurement of endometrial thickness with endovaginal ultrasound, and an endometrial biopsy for histologic review. Semen analyses were performed on recipients’ husbands and, when indicated, antisperm antibody testing was included. Couples were given the option of undergoing ICSI when there was clinical evidence of a possible fertilization failure, and ICSI only was performed on the day of retrieval. No ICSI was performed as a rescue procedure after retrieval day. For hormonal synchronization, the recipients underwent down-regulation with GnRH agonist (leuprolide acetate, 1 mg s.c. per day from midluteal phase) to achieve pituitary suppression if there was evidence of spontaneous ovarian function. For estrogen supplementation, we used increasing transdermal estradiol patches (0.1 mg) to simulate natural cycle levels, followed by progesterone in oil i.m. 25 mg on the day before oocyte donation and augmented to 50 mg i.m. daily for the subsequent days (7). Measurement of estradiol and progesterone levels and endometrial thickness assessed by ultrasonography was used in a similar way as in the preparatory cycle. For cryopreservation, only those recipients who received a frozen ET after a previous fresh ET were included in the study. The recipients who just received frozen ET because of synchronization or medical problems were excluded from the population studied. Vol. 73, No. 6, June 2000
TABLE 1 Patient and cycle data. Patient data
Results
Mean (⫾SD) recipient age in y Mean (⫾SD) donor age in y No. of donor cycles initiated No. of donor cancellations/no. of initiated cycles No. of donors completing oocyte retrievals No. of unshared donation cycles/no. of retrievals Mean (⫾SD) no. of oocytes received per recipient No. of recipients with no fertilized oocytes Total recipient cancellation ratea (cancelled/initiated)
40.9 ⫾ 4.4 28.1 ⫾ 3.7 249 8/249 (3.2%) 241 26/241 (10.8%) 8.3 ⫾ 3.5 13 39/511 (7.6%)
a
Total number of recipients with no transfer due to cycle conversion or no fertilization. Moomjy. Shared oocyte donation. Fertil Steril 2000.
Definition of Variables Pregnancy rate per recipient reflects the sum of all pregnancies with at least one fetal heartbeat divided by the total number of completed transfers. This measure is the potential for pregnancy that a recipient would anticipate. Pregnancy rate per donor retrieval reflects the sum of all pregnancies with at least one fetal heartbeat divided by the total number of completed donor retrievals. This measure is the potential for pregnancy that the center can anticipate per donor stimulation and completed retrieval. Ongoing pregnancy and delivery rate includes all completed deliveries and pregnancies in the second or third trimester divided by recipient transfer or donor retrieval as indicated. A biochemical pregnancy, considered as rise and fall of -hCG levels before 7 weeks’ gestation, was recorded as negative for pregnancy. Implantation rate is the sum of all fetal heartbeats divided by the sum of all embryos transferred. A miscarriage is the loss of the fetal heartbeat of a clinical pregnancy.
RESULTS The donors’ mean (⫾SD) age was 28.1 ⫾ 3.7 years; the recipients’ mean (⫾SD) age was 40.9 ⫾ 4.4 years. A total of 249 shared anonymous donor cycles were initiated, of which 241 retrievals occurred. The cancellation rate for donors, generally because of high response to ovarian stimulation, was 3.2% (8 of 249 patients). The need to convert from shared to unshared donation generally for low response with the cancellation of one recipient occurred in 10.8% (26 of 241 donors) of the recipient cycles. For 13 recipients, no fertilization occurred. The recipient cancellation rate for both cycle conversion to unshared donation and no fertilization combined was 39 of 511 cycles (7.6%). Each recipient received a mean (⫾SD) of 8.3 ⫾ 3.5 oocytes per donation cycle. Data are depicted in Table 1.
Recipient Outcome Measures In this study, 241 anonymous oocyte donation retrievals resulted in ET for 472 recipients. Fresh transfers were perFERTILITY & STERILITY威
formed in 424 recipients, and frozen ETs in 48 recipients (Table 2). Given recent implantation data for this center, recipient couples have been advised to accept two or three embryos at transfer. Before 1994, some transfers involved four embryos, given the lower implantation rate during that time. Clinical pregnancy rate per recipient fresh ET was 56.8%, with ongoing pregnancy and delivery rate of 49.7%. For recipients with frozen ET, these rates were 50% and 39.5%, respectively. The implantation rates were 31.8% and 26.1%, for fresh ET and frozen ET, respectively. The miscarriage rate was 12.4% for fresh ET and 20.8% for frozen ET. There were four ectopic pregnancies, which were considered negative for pregnancy in these statistics. Outcome data are depicted in Table 3.
Outcomes As Measured Per Donor Retrieval When calculated according to a single cohort of oocytes retrieved from a single donor, the donor cumulative pregnancy rate for all fresh and frozen ETs was 109.5%, and the ongoing pregnancy and delivery rate was 95.4%. This per donor pregnancy rate of ⬎100% is the result of shared donation that yielded an average of two recipient transfers per single donor retrieval. For fresh ET results alone, clinical pregnancy rate and ongoing pregnancy and delivery rate calculated per cohort of oocytes of a single donor retrieval were 100% and 87.5%, respectively. Conversion of a shared donation cycle to an unshared donation cycle occurred in 26 of 241 donor cycles (10.8%) (Table 1), because of low egg yield (19 recipients), for medical or personal reasons (5 recipients), and because of inadequate synchronization (2 recipients).
DISCUSSION The number of women with partial or complete ovarian failure requesting oocyte donation is far greater than the availability of women willing to participate in oocyte donation. Because of the rigorous testing for potential genetic or infectious diseases and because of the extraordinary commitment required, our experience has been that ⬍50% of the
TABLE 2 Transfer data per donor retrieval resulting from shared oocyte donation.
Fresh ET Frozen ET Fresh and frozen ET combined
Total number of recipient transfers
Total number of donors retrieved
424 48
241
1.75 0.20
472
241
1.95
Mean transfers per donor
Moomjy. Shared oocyte donation. Fertil Steril 2000.
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mize donor risks and medication exposure weighs in favor of continuing with shared oocyte donation.
TABLE 3 Outcome data for recipients of shared donor oocyte donation.
Clinical pregnancies Fresh ET Frozen ET Fresh ET ⫹ frozen ET Ongoing pregnancies and deliveries Fresh ET Frozen ET Fresh ET ⫹ frozen ET Implantation rate Fresh ET Frozen ET Fresh ET ⫹ frozen ET
No. of outcomes/total no. of ETs (%)
No. of outcomes/no. of retrievals (%)
241/424 (56.8) 24/48 (50.0) 264/472 (55.9)
241/241 (100) 24/40 (60.0) 264/241 (109.5)
211/424 (49.7) 19/48 (39.5) 230/472 (48.7)
211/241 (87.5) 19/40 (47.5) 230/241 (95.4)
430/1,350 (31.8) 36/138 (26.1) 466/1,488 (31.3)
Moomjy. Shared oocyte donation. Fertil Steril 2000.
donors starting the process of screening actually are approved to proceed to stimulation and retrieval. Because of this imbalance between need for donation and availability of donors, recipients often wait longer than expected until a matched donor is available. Shared oocyte donation has emerged as a more efficient use of this precious resource of human oocytes. From our series results, 90% of the time there was an adequate number of healthy mature oocytes available at the time of donation for two recipients. Because the mean number of oocytes received in shared donation is 8.3, it is anticipated that the recipient will receive the recommended fresh ET of two or three embryos to have a 57% chance of a clinical pregnancy. This form of oocyte disposition permits less exposure of donors per families completed. It has been our experience that almost all oocyte retrievals in anonymous donation cycles will result in a clinical pregnancy, taking into account both fresh and frozen recipient ET combined. Nevertheless, shared ovum donation does result in an overall reduction of embryos available for cryopreservation. It is recognized that many couples consider this a disadvantage. Ultimately, at our center, 48.2% of the pregnancies are multiple gestations and probably completed families. Although 51.8% of the pregnancies are singleton gestations, about one third to one half of our recipients already have one child at home. For 43% of the recipients who are not pregnant on a given fresh ET and for the 13% who happen to miscarry, an opportunity for a frozen ET in an expeditious fashion is highly desirable. To date, 30.3% of shared anonymous oocyte donation cycles have also provided for frozen embryos at our center. We believe that the responsibility to optimize donor management and to mini1168 Moomjy et al.
Shared oocyte donation: society’s benefits
Another advantage of this approach is that having two potential recipients per donor permits completion of ovarian stimulation and retrieval in the event that one recipient cancels her cycle for medical or personal reasons. There are concerns about increasing the possibility of inadvertent consanguinity brought about by the use of shared oocyte donation. Because some parents may choose not to disclose to their children their genetic origins when oocyte donation is used, it is remotely possible to have unknown consanguinity between individuals genetically related to the same oocyte donor. The risk of potential unknown consanguinity is not absent in unshared oocyte donation because donors may have their own children. This raises responsibility issues for the programs, to limit the number of donor attempts, for donor safety and to avoid future couples of unknowing genetic half-siblings. National guidelines by the American Society for Reproductive Medicine for prudent limitation of retrievals and pregnancies per donor are currently being debated. In addition, couples should be counseled about the rare possibility of unknown consanguinity, a risk that can be lessened with disclosure. There is still no consensus concerning the association between ovarian stimulation and epithelial ovarian carcinoma (8 –12), but it is clear that this theoretical risk is a concern. By means of shared oocyte donation, we have been able to decrease the population of donors exposed to ovarian stimulation for a given population of recipients. Alternatively, a conservative limit on total donation cycles per donor can be set to similarly reduce exposure to ovarian stimulation. This is an issue of importance when one must decide on risk exposures. Cost reduction with this form of treatment is obvious. By comparing costs between our program of shared oocyte donation and other oocyte donation programs in the region, we found that costs for shared donation are 39% lower than unshared donation. For anonymous oocyte donation, sharing of oocytes between two phenotypically matched recipients provides a good opportunity for the recipient to experience pregnancy, while keeping medical risks and discomforts to an absolute minimum for the donor group. Precious human oocytes are well utilized in shared oocyte donation. References 1. Ahuja KK, Mostyn BJ, Simons EG. Egg sharing and egg donation: attitudes of British egg donors and recipients. Hum Reprod 1997;12: 2845–52. 2. Ahuja KK, Simons EG, Fiamanya W, Dalton M, Armar NA, Kirkpatrick P, et al. Egg-sharing in assisted conception: ethical and practical considerations. Hum Reprod 1996;11:1126 –31. 3. Englert Y, Govaerts I. Oocyte donation: particular technical and ethical aspects. Hum Reprod 1998;13(Supp 2):90 –7. 4. Peskin BD, Austin C, Lisbona H, Goldfarb JM. Cost analysis of shared oocyte in vitro fertilization. Obstet Gynecol 1996;88:428 –30.
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5. Abdalla HI, Wren ME, Thomas A, Korea L. Age of the uterus does not affect pregnancy or implantation rates; a study of egg donation in women of different ages sharing oocytes from the same donor. Hum Reprod 1997;12:827–9. 6. Borini A, Bianchi L, Violini F, Maccolini A, Cattoli M, Flamigni C. Oocyte donation program: pregnancy and implantation rates in women of different ages sharing oocytes from single donor. Fertil Steril 1996; 65:94 –7. 7. Rosenwaks Z. Donor eggs: their application in modern reproductive technologies. Fertil Steril 1987;47:895–909. 8. Rossing MA, Daling JR, Weiss NS, Moore DE, Self SG. Ovarian tumors in a cohort of infertile women. N Engl J Med 1994;331:771– 6.
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9. Shushan A, Paltiel O, Iscovich J, Elchalal U, Peretz T, Schenker JG. Human menopausal gonadotropin and the risk of epithelial ovarian cancer. Fertil Steril 1996;65:13– 8. 10. Mosgaard BJ, Lidegaard O, Kruger Kjaer S, Schou G, Nyboe Andersen A. Infertility, fertility drugs, and invasive ovarian cancer: a case-control study. Fertil Steril 1997;67:1005–11. 11. Parazzini F, Negri E, La Vecchia C, Moroni S, Franceschi S, Crosignani PG. Treatment for infertility and risk of invasive epithelial ovarian cancer. Hum Reprod 1997;12:2159 – 61. 12. Mosgaard BJ, Lidegaard O, Nyboe Andersen A. The impact of parity, infertility and treatment with fertility drugs on the risk of ovarian cancer. Acta Obstet Gynecol Scand 1997;76:89 –95.
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