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Polycystic ovary syndrome patients as oocyte donors: the effect of ovarian stimulation protocol on the implantation rate of the recipient
FERTILITY AND STERILITY Copyright
Vol. 64, No, 3, September 1995
Printed on acid-free paper in U. S. A.
1995 American Society for Reproductive Medicine
Polycystic ovary syndrome patients as oocyte donors: the effect of ovarian stimulation protocol on the implantation rate of the recipient
Jacob Ashkenazi, M,D, Jacob Farhi, M.D. Raoul Orvieto, M.D. Roy Homburg, M.D.
Arie Dekel, M.D. Dov Feldberg, M.D. Zion Ben Rafael, M.D. *
Department of Obstetrics and Gynecology and Sherman Fertility Institute, Golda Meir Medical Center, Hasharon Hospital, Petah Tikva, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Objective: To evaluate the outcome of oocytes donated by women with polycystic ovarian syndrome (peOS) compared with oocytes donated by women with mechanical infertility. Design: A retrospective study. Patients: The outcome of 159 oocyte donation cycles with oocyte donated by peos patients were compared with 69 oocyte donation cycles with oocytes donated by patients with mechanical infertility. We compared the stimulation protocols in the donors to assess if the combination of GnRH analogue (GnRH-a), FSH, and hMG has an advantage over FSH and hMG alone with respect to their effect on fertilization and implantation rates in oocyte donation cycles. Results: When treated with GnRH-a, pregnancy rates in peos and mechanical infertility donors were higher than those treated with FSH and hMG alone. The comparison between peos and mechanical factor oocyte recipients revealed no significant difference in the pregnancy and abortion rates, but the oocytes of patients with peos that were exposed to GnRH-a had a significantly higher implantation rate than those not exposed to GnRH-a. Conclusions: Oocytes obtained from peos patients had a fertilization potential equal to oocytes obtained from mechanical infertility donors. Furthermore, because the oocytes of patients with peos exposed to GnRH-a had a significantly higher implantation rate, a detrimental role of high LH on oocyte quality seems probable. However, because peos has a high familial prevalence, some reservations may arise due to a possible propagation of the problem in the next generation of oocyte donation programs. Fertil Steril 1995;64:564-7 Key Words: Oocyte donation, peos, ovulation induction
Pregnancy resulting from oocyte donation was reported first in 1984 (1) and subsequently developed into a well-established mode of treatment for patients with primary or secondary ovarian failure. The relatively high success rate achieved by this procedure made oocyte donation an attractive alternative for the treatment of other indications, such as low responders to superovulation, women at age >40 years, or couples suffering from familial genetic disorders (2, 3). This expansion of the indication for oocyte donation has led to a further demand for doReceived October 10, 1994; revised and accepted March 14, 1995. * Reprint requests: Zion Ben Rafael M.D., Department of Obstetrics and Gynecology, Golda Meir Medical Center, Hasharon Hospital, Petah Tiqva 49372, Israel (FAX: 972--:3-9372445).
564
Ashkenazi et a1. PCOS patients as oocyte donors
nor oocytes. Moreover, because the regulations in Israel require that only women who themselves need IVF treatment may be donors, patients with polycystic ovarian syndrome (PCOS) who frequently had a relatively high number of oocytes retrieved became the most important source for oocyte donation. In this study we compared the results of oocytes donated by PCOS women undergoing IVF with results of oocytes donated by women with mechanical infertility. We examined the fertilization and implantation rates and the effect of GnRH analogue (GnRH-a) on the overall results in the donors and recipient. MATERIALS AND METHODS
The study group was selected from an IVF donor population who underwent treatment during the Fertility and Sterility
Table 1 Clinical and Laboratory Characteristics of PCOS and Mechanical Group of Patients
No. of patients Age (y) Menstrual disorder Hirsutism Obesity (body mass index> 27) LH (mIU/mL)t FSH (mIU/mL)t LH:FSH PRL (ng/mL)t T (ng/mL)t
PC OS
Mechanical
79 31.5 :!: 3.1* 53 51 67 23.7 :!: 9.1 7.1 :!: 3.0 3.7 :!: 1.9 23.1 ::': 12 0.47 ::': 0.23
66 29.8:!: 4.3 0 0 11 6.4 :!: 2.1 6.2 :!: 1.8 1.1 ::': 0.7
* Values are means::': SD. t Conversion factor to SI unit, 1.00. t Conversion factor to SI unit, 3.467.
last 3 years. A total of 79 patients with PCOS and 66 mechanically infertile donors (who were treated over 160 cycles) were identified and compared. There no other infertility factors other than the one given for each patient, i.e., no evidence of endometriosis or male factor in all patients, no mechanical factor in the PCOS group, and no evidence of polycystic ovaries in the mechanical group. The recipient population comprised 191 women who underwent 228 cycles of oocyte donation. Polycystic ovarian syndrome was diagnosed by its characteristic appearance on vaginal ultrasound (US) (4), and an LH:FSH ratio >2. Some patients also had high serum androgen concentrations (total T). Obesity was defined as body mass index [weight (kg)/height (m 2)] >27 and hirsutism was defined by both patient perception of having superfluous hair and clinical examination revealing excessive body hair (Table 1). All oocytes were donated in synchrony between the donor and the recipient. Frozen cycles were excluded from the study. Stimulation protocols of oocyte donors consisted of either FSH and hMG only, or a combination of GnRH-a for down-regulation and then FSH and hMG. The FSH and hMG-only protocol was administered in a dose of three ampules per day of FSH (Metrodin; Teva, Petah Tiqva, Israel) from day 3 to 5 of the cycle, followed by three ampules of hMG (Pergonal; Teva) from day 6, which subsequently was adjusted according to the hormonal response of the individual patient. The combined GnRH-a, FSH, and hMG protocol consisted of a single injection of 3.75 mg GnRH-a (Decapeptyl DTRp6 microcapsules; Ferring, Malmo, Sweden) followed by ovarian stimulation on day 15 to 19 after ovarian down-regulation was ascertained (LH < 7 mIU/mL [conversion factor to SI unit, 1.00]; E2 < 19.8 pg/mL «73 pmol/mL); P < 0.2 nglmL «0.6 nmol/mL) and no ovarian cysts were observed on US. Three ampules of FSH were Vol. 64, No.3, September 1995
given for 3 days, followed by three ampules of hMG daily, and adjusted according to the response. Treatment was monitored by ultrasonographic scanning and plasma E2 and P measurements. Oocytes were retrieved 33 to 36 hours after injection of 10,000 IU hCG (Chorigon; Teva). The group of recipients (n = 191) included patients with premature ovarian failure, menopausal and perimenopausal patients, and those who had failed to achieve adequate ovarian response in previous IVF attempts. The protocol for endometrial preparation in recipients was 6 mg/d E2 valerate (Progyluton; Schering, Berlin, Germany) for 5 to 25 days. In patients with spontaneous menstruation, treatment with E2 valerate was started in the 3rd day of the cycle. Estradiol valerate was given to the recipients in synchrony with the potential donor cycle until the day of oocyte aspiration, when 200 mg/d P in the form of vaginal suppositories (micronized P, privately manufactured) was given and E2 was reduced to 4 mg daily. Endometrial thickness >9 mm with characteristic three-layer appearance on the day of hCG was considered a satisfactory response. Embryo transfer was performed after 48 hours in the donors and 72 hours after oocyte retrieval in the recipients. Eleven days thereafter a quantitative serum ,B-hCG test was obtained. The recipients were divided into two groups: group 1 comprised 145 patients receiving oocytes from donors with PCOS and group 2 comprised 56 patients receiving oocytes from donors with mechanical factor. The results are expressed as means::!:: SD. The data were analyzed with the X2 test or Fisher's exact test where appropriate. We accept significance whenever P was :=;0.05.
RESULTS Table 2 depicts comparison between different protocols of induction of ovulation within each group of donors and between the same protocol of ovulation induction in different groups of donors. Donors treated with a combination of GnRH-a and FSH and hMG had a tendency toward an higher pregnancy rate (PR) when compared with donors treated with FSH and hMG. However, these differences were not statistically significant. The overall implantation rate per embryo did not differ in PCOS compared with mechanical factor donors (6.0% and 5.9%, respectively). Table 3 illustrates the results of IVF treatment in the recipients. Mean duration of E2 valerate therapy and mean endometrial thickness before adding P were similar in the group with PC OS-derived oocyte recipients compared with mechanical factor-derived oocyte recipients (13.4 ::!:: 6.5 versus 14.7 ::!:: 7.1 days Ashkenazi et al. peDS patients as oocyte donors
565
Table 2
Results of IVF Treatment in
peos and Mechanical Donor Patients peos patients (n
No. of patients No. of cycles No. oocytes retrieved*t No. of embryos*t Implantation rate per embryot (%) PR per transfert (%)
=
66)
FSH + hMG + GnRH-a
FSH + hMG
FSH + hMG + GnRH-a
39 46 12.6 ± 5.8 4.2 ± 0.9
40 48 15.4 ± 7.4 4.1 ± 1.1
35 35 10.3 ± 3.4 4.2 ± 0.7
31 31 12.9 ± 6.8 4.3 ± 0.9
4.1 (8/192) 15.2 (7/46)
7.7 (7/219) 31.2 (5/48)
5.8 (9/153) 22.8 (8/35)
5.9 (10/167) 32.2 (0/31)
t Not significant, P > 0.05.
and 9.0 ± 0.9 versus 9.2 ± 1.1 mm, respectively; mean ± SD). The overall results were not different in the group with PeOS-derived oocyte recipients compared with mechanical factor-derived oocyte recipients regarding pregnancy and abortion rates (power calculations for type II error P < 0.05). When the results in the recipients were examined according to the ovulation induction protocol (i.e., with or without GnRH-a) of the donors, no differences were found in pregnancy or abortion rates. However, in the recipients, the oocytes of patients with peos that were exposed to GnRH-a had a significantly higher implantation rate compared with those that were not exposed to GnRH-a (11.7% and 6.6%, respectively; P < 0.05). DISCUSSION
The success of IVF is determined by three major factors: quality of gametes, adequate endometrial receptivity, and the synchronization of both. Endometrial receptivity depends mainly on induction of adequate secretory changes with P in an endometrium appropriately primed by estrogen (5). Because, in an oocyte donation cycle, all recipients are exposed to the same hormone replacement therapy and the implantation window is similar (2), the results of the oocyte donation cycle depend primarily on the qual-
ity of the gametes and the resulting embryos (2, 5). Although oocyte quality has a major impact on the success of oocyte donation, oocyte donor selection is based on minimal criteria such as age <38 years, no medical or psychiatric illness, and no history of familial genetic disorders (2). This probably results from the restricted source of oocytes for oocyte donation programs. The success of oocyte donation has been related to younger donors (5-7), high fertilization rate, and oocyte quality (6), whereas the infertility of donors has been suggested as being a detrimental factor. In our IVF unit, according to local regulations, oocyte donation are obtained only from infertile patients undergoing IVF. In this study the overall PR per cycle of recipients was 23.7%, lower than that of 38.6% reported when the oocytes were donated by fertile women (5), who are probably younger, with a better-quality oocyte (2, 8). Because peos patients produce a large number of eggs, of which some can be donated, we studied their quality in comparison to mechanical factor infertile donors. We found no differences in the implantation or abortion rate between the two groups of recipients. Because endometrial preparation was similar and no sperm abnormalities were apparent in the two groups, the obtained fertilization and im-
Results of IVF Treatment in the Recipients According to Ovulation Induction Protocol of Donors Recipients from
No. of patients No. of cycles No. of oocytes donated* No. of embryos transferred* Implantation rate per embryo (%) PR per transfer (%) Abortion rate per patient (%)
Ashkenazi et al.
peos donors
Total
FSH + hMG
145 159 4.4 ± 0.9 2.6 ± 0.9
70 77
23.2 (371159)
4.4 ± 0.7 2.6 ± 0.9 6.6 04/212) 18.1 (4177)
13.5 (5/37)
21.4 (3/14)
9.2 (40/433)
* Values are means ± SD. t Not significant, P > 0.05. 566
Mechanical patients (n
FSH + hMG
* Values are means ± SD.
Table 3
= 79)
peos patients as oocyte donors
FSH + hMG + GnRH-a 75 82 4.4 ± 0.6t 2.7 ± 0.8t 11.7:1: (26/222)
28.0t (23/82) 8.7t (2/23)
Recipients from mechanical donors Total
FSH + hMG
FSH + hMG + GnRH-a
56 69
28 36
3.2 ± 0.7 2.5 ± 0.8
2.8 ± 0.6 2.1 ± 0.5 11.6 (9177)
28 33 3.6 ± 0.9t 2.8 ± 0.8t 9.4t (9/95) 27.2t (9/33) 33.3t (3/9)
10.5 (18/172) 24.6 (17/69) 29.4 (5/17)
22.2 (8/36) 25.0 (2/8)
:I: P < 0.05 compared with recipients from peos donors treated with FSH + hMG. Fertility and Sterility
plantation rates probably indicate oocyte quality. The similarity in the results of both groups ofrecipients suggest that oocytes obtained from peas patients have a fertilization potential equal to oocytes obtained from mechanical donors. However, peas is the most common endocrine disorder with an obscure etiology, and its high prevalence among families might imply a genetic basis with highly variable penetration. Therefore, despite the fact that this study indicates that peas patients are a good source for oocytes, some reservations may arise due to possible propagation of the problem to the next generation. avum donation cycles present a unique model of oocyte and embryo quality evaluation for implantation potential. This is due to similar priming of the endometrium and the timing of ET in all the recipients. Analysis of oocyte donation results within the group of recipients from peas donors indicated that implantation rate depends on the protocol of ovulation induction ofthe donor. In the recipients, oocytes exposed to GnRH-a had a significantly higher implantation rate than those that were not exposed to GnRH-a and ovarian stimulation was by gonadotropins only (Table 3). A similar trend, but without significant statistical difference, was observed in the results of oocyte donation in the recipients of oocytes from mechanical factor donors. The impact of GnRHa on oocyte quality is still a controversial issue and the reason for the improved results in recipients with oocytes derived from GnRH -a exposure still is unknown. Although decreased LH in peas patients treated with GnRH-a during the follicular phase was implicated in a better success rate and lower abortion rate (9), others have reported that exposure to GnRH-a during ovarian stimulation did not appear to influence the implantation rate of embryos that survived thawing (7.1% implantation rate per embryo) (8). However, our results indicate an improved implantation rate in peas patients exposed to GnRH-a, which may suggest a better oocyte quality during ovulation induction with GnRH-a that might
Vol. 64, No.3, September 1995
be attributed to the reduction in high LH levels and the elimination of its detrimental effect on the 00cytes. aur results in regard to the performance of oocyte donation cycles are in accordance with previous reports (10). It is noteworthy that the success rate of the donors is not compromised by oocyte donation. The overall success rate of donors (25%) and implantation rate per ET (6%) were not different in peas and mechanical donors and were similar to the results obtained in our unit in nondonor mechanically infertile women of the same age. REFERENCES 1. Lutjen P, Trounson A, Leeton J, Findlay J, Wood C, Renou P. The establishment and maintenance of pregnancy using in vitro fertilization and embryo donation in a patient with premature ovarian failure. Nature 1984;307:174-5. 2. Serhal P. Oocyte donation and surrogacy. Br Med J 1990;46:796-812. 3. Serhal PF, Craft IL. Oocyte donation in 61 patients. Lancet 1989; 1:1185-7. 4. Adams J, Franks S, Polson DW, Mason HD, Abdulwaid N, Tucker M, et al. Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotrophin releasing hormone. Lancet 1985;2:1375-8. 5. Serhal PF, Craft IL. Oocyte donation in 61 patients. Lancet 1989;1:1185-7. 6. Burton G, Abdalla HI, Kirland A, Studd JWW. The role of oocyte donation in women who are unsuccessful with in vitro fertilization treatment. Hum Reprod 1992;7:1103-5. 7. Edwards R, Morcos S, Macnamee M, Balmaceda J, Walters D, Asch R. High fecundity of amenorrhoeic women in embryo transfer program. Lancet 1991;338:292-4. 8. de Ziegler D, Frydman R. Different implantation rates after transfers of cryopreserved embryos originating from donated oocytes or from regular in vitro fertilization. Fertil Steril 1990;54:682-8. 9. Homburg R, Levy T, Berkovitz D, Farhi J, Feldberg D, Ashkenazi J, et al. Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome. Fertil Steril 1993;59:527 -31. 10. Power M, Babaer R, Abdalla H, Kirland A, Leonard T, Studd JW. A comparison of the attitude of volunteer donors and infertile patient donors on an ovum donation programme. Hum Reprod 1990;5:352-5.
Ashkenazi et aI. peas patients as oocyte donors
567
Vol. 64, No, 3, September 1995
Printed on acid-free paper in U. S. A.
1995 American Society for Reproductive Medicine
Polycystic ovary syndrome patients as oocyte donors: the effect of ovarian stimulation protocol on the implantation rate of the recipient
Jacob Ashkenazi, M,D, Jacob Farhi, M.D. Raoul Orvieto, M.D. Roy Homburg, M.D.
Arie Dekel, M.D. Dov Feldberg, M.D. Zion Ben Rafael, M.D. *
Department of Obstetrics and Gynecology and Sherman Fertility Institute, Golda Meir Medical Center, Hasharon Hospital, Petah Tikva, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Objective: To evaluate the outcome of oocytes donated by women with polycystic ovarian syndrome (peOS) compared with oocytes donated by women with mechanical infertility. Design: A retrospective study. Patients: The outcome of 159 oocyte donation cycles with oocyte donated by peos patients were compared with 69 oocyte donation cycles with oocytes donated by patients with mechanical infertility. We compared the stimulation protocols in the donors to assess if the combination of GnRH analogue (GnRH-a), FSH, and hMG has an advantage over FSH and hMG alone with respect to their effect on fertilization and implantation rates in oocyte donation cycles. Results: When treated with GnRH-a, pregnancy rates in peos and mechanical infertility donors were higher than those treated with FSH and hMG alone. The comparison between peos and mechanical factor oocyte recipients revealed no significant difference in the pregnancy and abortion rates, but the oocytes of patients with peos that were exposed to GnRH-a had a significantly higher implantation rate than those not exposed to GnRH-a. Conclusions: Oocytes obtained from peos patients had a fertilization potential equal to oocytes obtained from mechanical infertility donors. Furthermore, because the oocytes of patients with peos exposed to GnRH-a had a significantly higher implantation rate, a detrimental role of high LH on oocyte quality seems probable. However, because peos has a high familial prevalence, some reservations may arise due to a possible propagation of the problem in the next generation of oocyte donation programs. Fertil Steril 1995;64:564-7 Key Words: Oocyte donation, peos, ovulation induction
Pregnancy resulting from oocyte donation was reported first in 1984 (1) and subsequently developed into a well-established mode of treatment for patients with primary or secondary ovarian failure. The relatively high success rate achieved by this procedure made oocyte donation an attractive alternative for the treatment of other indications, such as low responders to superovulation, women at age >40 years, or couples suffering from familial genetic disorders (2, 3). This expansion of the indication for oocyte donation has led to a further demand for doReceived October 10, 1994; revised and accepted March 14, 1995. * Reprint requests: Zion Ben Rafael M.D., Department of Obstetrics and Gynecology, Golda Meir Medical Center, Hasharon Hospital, Petah Tiqva 49372, Israel (FAX: 972--:3-9372445).
564
Ashkenazi et a1. PCOS patients as oocyte donors
nor oocytes. Moreover, because the regulations in Israel require that only women who themselves need IVF treatment may be donors, patients with polycystic ovarian syndrome (PCOS) who frequently had a relatively high number of oocytes retrieved became the most important source for oocyte donation. In this study we compared the results of oocytes donated by PCOS women undergoing IVF with results of oocytes donated by women with mechanical infertility. We examined the fertilization and implantation rates and the effect of GnRH analogue (GnRH-a) on the overall results in the donors and recipient. MATERIALS AND METHODS
The study group was selected from an IVF donor population who underwent treatment during the Fertility and Sterility
Table 1 Clinical and Laboratory Characteristics of PCOS and Mechanical Group of Patients
No. of patients Age (y) Menstrual disorder Hirsutism Obesity (body mass index> 27) LH (mIU/mL)t FSH (mIU/mL)t LH:FSH PRL (ng/mL)t T (ng/mL)t
PC OS
Mechanical
79 31.5 :!: 3.1* 53 51 67 23.7 :!: 9.1 7.1 :!: 3.0 3.7 :!: 1.9 23.1 ::': 12 0.47 ::': 0.23
66 29.8:!: 4.3 0 0 11 6.4 :!: 2.1 6.2 :!: 1.8 1.1 ::': 0.7
* Values are means::': SD. t Conversion factor to SI unit, 1.00. t Conversion factor to SI unit, 3.467.
last 3 years. A total of 79 patients with PCOS and 66 mechanically infertile donors (who were treated over 160 cycles) were identified and compared. There no other infertility factors other than the one given for each patient, i.e., no evidence of endometriosis or male factor in all patients, no mechanical factor in the PCOS group, and no evidence of polycystic ovaries in the mechanical group. The recipient population comprised 191 women who underwent 228 cycles of oocyte donation. Polycystic ovarian syndrome was diagnosed by its characteristic appearance on vaginal ultrasound (US) (4), and an LH:FSH ratio >2. Some patients also had high serum androgen concentrations (total T). Obesity was defined as body mass index [weight (kg)/height (m 2)] >27 and hirsutism was defined by both patient perception of having superfluous hair and clinical examination revealing excessive body hair (Table 1). All oocytes were donated in synchrony between the donor and the recipient. Frozen cycles were excluded from the study. Stimulation protocols of oocyte donors consisted of either FSH and hMG only, or a combination of GnRH-a for down-regulation and then FSH and hMG. The FSH and hMG-only protocol was administered in a dose of three ampules per day of FSH (Metrodin; Teva, Petah Tiqva, Israel) from day 3 to 5 of the cycle, followed by three ampules of hMG (Pergonal; Teva) from day 6, which subsequently was adjusted according to the hormonal response of the individual patient. The combined GnRH-a, FSH, and hMG protocol consisted of a single injection of 3.75 mg GnRH-a (Decapeptyl DTRp6 microcapsules; Ferring, Malmo, Sweden) followed by ovarian stimulation on day 15 to 19 after ovarian down-regulation was ascertained (LH < 7 mIU/mL [conversion factor to SI unit, 1.00]; E2 < 19.8 pg/mL «73 pmol/mL); P < 0.2 nglmL «0.6 nmol/mL) and no ovarian cysts were observed on US. Three ampules of FSH were Vol. 64, No.3, September 1995
given for 3 days, followed by three ampules of hMG daily, and adjusted according to the response. Treatment was monitored by ultrasonographic scanning and plasma E2 and P measurements. Oocytes were retrieved 33 to 36 hours after injection of 10,000 IU hCG (Chorigon; Teva). The group of recipients (n = 191) included patients with premature ovarian failure, menopausal and perimenopausal patients, and those who had failed to achieve adequate ovarian response in previous IVF attempts. The protocol for endometrial preparation in recipients was 6 mg/d E2 valerate (Progyluton; Schering, Berlin, Germany) for 5 to 25 days. In patients with spontaneous menstruation, treatment with E2 valerate was started in the 3rd day of the cycle. Estradiol valerate was given to the recipients in synchrony with the potential donor cycle until the day of oocyte aspiration, when 200 mg/d P in the form of vaginal suppositories (micronized P, privately manufactured) was given and E2 was reduced to 4 mg daily. Endometrial thickness >9 mm with characteristic three-layer appearance on the day of hCG was considered a satisfactory response. Embryo transfer was performed after 48 hours in the donors and 72 hours after oocyte retrieval in the recipients. Eleven days thereafter a quantitative serum ,B-hCG test was obtained. The recipients were divided into two groups: group 1 comprised 145 patients receiving oocytes from donors with PCOS and group 2 comprised 56 patients receiving oocytes from donors with mechanical factor. The results are expressed as means::!:: SD. The data were analyzed with the X2 test or Fisher's exact test where appropriate. We accept significance whenever P was :=;0.05.
RESULTS Table 2 depicts comparison between different protocols of induction of ovulation within each group of donors and between the same protocol of ovulation induction in different groups of donors. Donors treated with a combination of GnRH-a and FSH and hMG had a tendency toward an higher pregnancy rate (PR) when compared with donors treated with FSH and hMG. However, these differences were not statistically significant. The overall implantation rate per embryo did not differ in PCOS compared with mechanical factor donors (6.0% and 5.9%, respectively). Table 3 illustrates the results of IVF treatment in the recipients. Mean duration of E2 valerate therapy and mean endometrial thickness before adding P were similar in the group with PC OS-derived oocyte recipients compared with mechanical factor-derived oocyte recipients (13.4 ::!:: 6.5 versus 14.7 ::!:: 7.1 days Ashkenazi et al. peDS patients as oocyte donors
565
Table 2
Results of IVF Treatment in
peos and Mechanical Donor Patients peos patients (n
No. of patients No. of cycles No. oocytes retrieved*t No. of embryos*t Implantation rate per embryot (%) PR per transfert (%)
=
66)
FSH + hMG + GnRH-a
FSH + hMG
FSH + hMG + GnRH-a
39 46 12.6 ± 5.8 4.2 ± 0.9
40 48 15.4 ± 7.4 4.1 ± 1.1
35 35 10.3 ± 3.4 4.2 ± 0.7
31 31 12.9 ± 6.8 4.3 ± 0.9
4.1 (8/192) 15.2 (7/46)
7.7 (7/219) 31.2 (5/48)
5.8 (9/153) 22.8 (8/35)
5.9 (10/167) 32.2 (0/31)
t Not significant, P > 0.05.
and 9.0 ± 0.9 versus 9.2 ± 1.1 mm, respectively; mean ± SD). The overall results were not different in the group with PeOS-derived oocyte recipients compared with mechanical factor-derived oocyte recipients regarding pregnancy and abortion rates (power calculations for type II error P < 0.05). When the results in the recipients were examined according to the ovulation induction protocol (i.e., with or without GnRH-a) of the donors, no differences were found in pregnancy or abortion rates. However, in the recipients, the oocytes of patients with peos that were exposed to GnRH-a had a significantly higher implantation rate compared with those that were not exposed to GnRH-a (11.7% and 6.6%, respectively; P < 0.05). DISCUSSION
The success of IVF is determined by three major factors: quality of gametes, adequate endometrial receptivity, and the synchronization of both. Endometrial receptivity depends mainly on induction of adequate secretory changes with P in an endometrium appropriately primed by estrogen (5). Because, in an oocyte donation cycle, all recipients are exposed to the same hormone replacement therapy and the implantation window is similar (2), the results of the oocyte donation cycle depend primarily on the qual-
ity of the gametes and the resulting embryos (2, 5). Although oocyte quality has a major impact on the success of oocyte donation, oocyte donor selection is based on minimal criteria such as age <38 years, no medical or psychiatric illness, and no history of familial genetic disorders (2). This probably results from the restricted source of oocytes for oocyte donation programs. The success of oocyte donation has been related to younger donors (5-7), high fertilization rate, and oocyte quality (6), whereas the infertility of donors has been suggested as being a detrimental factor. In our IVF unit, according to local regulations, oocyte donation are obtained only from infertile patients undergoing IVF. In this study the overall PR per cycle of recipients was 23.7%, lower than that of 38.6% reported when the oocytes were donated by fertile women (5), who are probably younger, with a better-quality oocyte (2, 8). Because peos patients produce a large number of eggs, of which some can be donated, we studied their quality in comparison to mechanical factor infertile donors. We found no differences in the implantation or abortion rate between the two groups of recipients. Because endometrial preparation was similar and no sperm abnormalities were apparent in the two groups, the obtained fertilization and im-
Results of IVF Treatment in the Recipients According to Ovulation Induction Protocol of Donors Recipients from
No. of patients No. of cycles No. of oocytes donated* No. of embryos transferred* Implantation rate per embryo (%) PR per transfer (%) Abortion rate per patient (%)
Ashkenazi et al.
peos donors
Total
FSH + hMG
145 159 4.4 ± 0.9 2.6 ± 0.9
70 77
23.2 (371159)
4.4 ± 0.7 2.6 ± 0.9 6.6 04/212) 18.1 (4177)
13.5 (5/37)
21.4 (3/14)
9.2 (40/433)
* Values are means ± SD. t Not significant, P > 0.05. 566
Mechanical patients (n
FSH + hMG
* Values are means ± SD.
Table 3
= 79)
peos patients as oocyte donors
FSH + hMG + GnRH-a 75 82 4.4 ± 0.6t 2.7 ± 0.8t 11.7:1: (26/222)
28.0t (23/82) 8.7t (2/23)
Recipients from mechanical donors Total
FSH + hMG
FSH + hMG + GnRH-a
56 69
28 36
3.2 ± 0.7 2.5 ± 0.8
2.8 ± 0.6 2.1 ± 0.5 11.6 (9177)
28 33 3.6 ± 0.9t 2.8 ± 0.8t 9.4t (9/95) 27.2t (9/33) 33.3t (3/9)
10.5 (18/172) 24.6 (17/69) 29.4 (5/17)
22.2 (8/36) 25.0 (2/8)
:I: P < 0.05 compared with recipients from peos donors treated with FSH + hMG. Fertility and Sterility
plantation rates probably indicate oocyte quality. The similarity in the results of both groups ofrecipients suggest that oocytes obtained from peas patients have a fertilization potential equal to oocytes obtained from mechanical donors. However, peas is the most common endocrine disorder with an obscure etiology, and its high prevalence among families might imply a genetic basis with highly variable penetration. Therefore, despite the fact that this study indicates that peas patients are a good source for oocytes, some reservations may arise due to possible propagation of the problem to the next generation. avum donation cycles present a unique model of oocyte and embryo quality evaluation for implantation potential. This is due to similar priming of the endometrium and the timing of ET in all the recipients. Analysis of oocyte donation results within the group of recipients from peas donors indicated that implantation rate depends on the protocol of ovulation induction ofthe donor. In the recipients, oocytes exposed to GnRH-a had a significantly higher implantation rate than those that were not exposed to GnRH-a and ovarian stimulation was by gonadotropins only (Table 3). A similar trend, but without significant statistical difference, was observed in the results of oocyte donation in the recipients of oocytes from mechanical factor donors. The impact of GnRHa on oocyte quality is still a controversial issue and the reason for the improved results in recipients with oocytes derived from GnRH -a exposure still is unknown. Although decreased LH in peas patients treated with GnRH-a during the follicular phase was implicated in a better success rate and lower abortion rate (9), others have reported that exposure to GnRH-a during ovarian stimulation did not appear to influence the implantation rate of embryos that survived thawing (7.1% implantation rate per embryo) (8). However, our results indicate an improved implantation rate in peas patients exposed to GnRH-a, which may suggest a better oocyte quality during ovulation induction with GnRH-a that might
Vol. 64, No.3, September 1995
be attributed to the reduction in high LH levels and the elimination of its detrimental effect on the 00cytes. aur results in regard to the performance of oocyte donation cycles are in accordance with previous reports (10). It is noteworthy that the success rate of the donors is not compromised by oocyte donation. The overall success rate of donors (25%) and implantation rate per ET (6%) were not different in peas and mechanical donors and were similar to the results obtained in our unit in nondonor mechanically infertile women of the same age. REFERENCES 1. Lutjen P, Trounson A, Leeton J, Findlay J, Wood C, Renou P. The establishment and maintenance of pregnancy using in vitro fertilization and embryo donation in a patient with premature ovarian failure. Nature 1984;307:174-5. 2. Serhal P. Oocyte donation and surrogacy. Br Med J 1990;46:796-812. 3. Serhal PF, Craft IL. Oocyte donation in 61 patients. Lancet 1989; 1:1185-7. 4. Adams J, Franks S, Polson DW, Mason HD, Abdulwaid N, Tucker M, et al. Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotrophin releasing hormone. Lancet 1985;2:1375-8. 5. Serhal PF, Craft IL. Oocyte donation in 61 patients. Lancet 1989;1:1185-7. 6. Burton G, Abdalla HI, Kirland A, Studd JWW. The role of oocyte donation in women who are unsuccessful with in vitro fertilization treatment. Hum Reprod 1992;7:1103-5. 7. Edwards R, Morcos S, Macnamee M, Balmaceda J, Walters D, Asch R. High fecundity of amenorrhoeic women in embryo transfer program. Lancet 1991;338:292-4. 8. de Ziegler D, Frydman R. Different implantation rates after transfers of cryopreserved embryos originating from donated oocytes or from regular in vitro fertilization. Fertil Steril 1990;54:682-8. 9. Homburg R, Levy T, Berkovitz D, Farhi J, Feldberg D, Ashkenazi J, et al. Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome. Fertil Steril 1993;59:527 -31. 10. Power M, Babaer R, Abdalla H, Kirland A, Leonard T, Studd JW. A comparison of the attitude of volunteer donors and infertile patient donors on an ovum donation programme. Hum Reprod 1990;5:352-5.
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