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Therapeutic donor insemination (TDI) in advanced reproductive aged women: Impact of cycle type on success
MATERIALS AND METHODS: We examined the clinical records of 1099 consecutive women of reproductive age (range: 15–54 years) with benign ovarian cysts who underwent surgical treatment. Age of patients at time of surgery, sites and sizes of ovarian cysts were recorded. Cyst diameter was assessed by ultrasound examination in the month before surgery. The data were abstracted from a continuously updated database of women undergoing surgery in our institution. Women who had undergone previous abdominal surgery, except appendectomy, were excluded. ANOVA and one-way analysis of variance on ranks were used as appropriate. The 2-test was used to compare observed and expected events. RESULTS: Forty-four women with cyst of different histology in the same ovary or bilaterally were excluded from the analysis. Accordingly, the final study population included 1055 women. Patients with serous cysts were significantly older that those with endometriotic, dermoid, and paraovarian cysts (p⬍0.001). Dermoid cysts were unilateral in 202 (91.4%) women and bilateral in 19 (8.6%) patients. Among the women with unilateral dermoid cysts, 55.0% had left-sided cyst and 45.1% had right-sided cyst (not significant, p⫽0.159). Torsion occurred in 6 women with dermoid cysts; cysts undergoing torsion were significantly larger (p⫽0.004) than those that did not undergo torsion. Unilateral endometriotic cysts were found more frequently on the left ovary (n ⫽ 275, 59.9%) than on the right ovary (n ⫽ 184, 40.1%) (p⬍0.001; 18.041, 2). Serous, mucinous, and paraovarian cysts were equally distributed on both sides. Bilateral cysts were significantly more frequent in women with endometriotic cysts (19.3%, 95% CI 16.2– 22.8%) than in subjects with non-endometriotic cysts (8.4%, 95% CI 6.1–11.3%) (p⬍0.001, OR 2.60, 95% CI 1.78 –3.80). No significant difference was observed in the cyst diameter in right and left-sided cysts in each histologic group. CONCLUSION: Dermoid cysts as well as serous, mucinous, and paraovarian cysts are equally distributed on both sides. This finding is in contrast with previous reports suggesting a predisposition of dermoid cysts to a right lateral distribution. The presence of bilateral lesions should always be investigated in women with ovarian endometriosis. Supported by: None
P-15 Therapeutic donor insemination (TDI) in advanced reproductive aged women: Impact of cycle type on success. S. Ghadir, A. Huang, E. Mor, A. H. Decherney, R. P. Buyalos, K. L. Durinzi. David Geffen School of Medicine at UCLA, Los Angeles, CA; Keck School of Medicine at USC, Los Angeles, CA; Kaiser Permanente Medical Center, Los Angeles, CA. OBJECTIVE: Currently, single women who seek fertility rely on sperm donation and TDI for conception. It is possible that with advancing reproductive age these women will benefit from the use of superovulation in combination with TDI to increase their overall pregancy success. To test this hypothesis we compared pregnancy rates following different superovulation regimens in single normo-ovulatory women ages 35– 43 years undergoing TDI. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Subjects included all consecutive women presenting between 1/1/96 and 12/31/01 at two large communitybased hospitals for TDI. Subjects were all single and without a male partner, older than 35 yrs, eumenorrheic, and with tubal patency confirmed by hysterosalpingography. Subjects began treatment with TDI alone, and were advanced to TDI plus superovulation (see below) if not pregnant. Superovulation consisted of clomiphene citrate (CC) 100 mg/day 3–7 of the cycle(CC⫹TDI), followed by either human menopausal gonadotropin (hMG) 150 IU/day as the starting dose (hMG⫹TDI) or a combination of CC 100 mg on cycle days 3–7 plus hMG 150 IU initiated on cycle day 8 (CC⫹hMG⫹TDI). TDI was performed 12–14 hours following timed ovulation, as determined by an ovulation prediction kit in unstimulated cycles (TDI only), or 34 –36 hours following hCG 10,000 IU in stimulated cycles. The main outcome variable was clinical pregnancy rate per cycle, stratified according to treatment type. Statistical analysis was by Student’s t test and chi-square test. RESULTS: Thirty-six women, mean age 39.1 ⫾ 2.4 yrs (range: 35 to 43 yrs), met entry criteria and underwent a total of 148 cycles of TDI; 72% had prior conceptions. Twenty-five cycles were unstimulated (TDI alone), 70 were CC⫹TDI, 47 were hMG⫹TDI, and 6 were CC⫹hMG⫹TDI. Mean patient ages were similar for TDI alone CC⫹TDI, hMG⫹TDI, and CC⫹hMG⫹TDI cycles (39.2 ⫾ 2.6 yrs, 38.5 ⫾ 2.1 yrs, 38.6 ⫾ 2.4 yrs, and
FERTILITY & STERILITY威
37.5 ⫾ 0.7 yrs, respectively) (p⫽NS). Overall, mean cycle day 3 FSH and estradiol levels were 8.3 ⫾ 4.8 mlU/mL and 47.8 ⫾ 21.6 pg/mL, respectively, while levels were similar among the 4 treatment groups (p⫽NS). The overall per cycle clinical pregnancy rate was 11.4% (95% CI: 7,18%). The overall delivery rate per cycle was 7.4%. The clinical pregnancy rate observed in cycles utilizing TDI only (11.5%; 95% CI: 3, 34%), was similar to the per cycle pregnancy rate observed in CC/TDI cycles (8.6%; 95% CI: 3, 18%) (OR⫽ 0.7), hMG/TDI cycles (14.9%; 95% CI: 7–28%) (OR⫽1.3), and CC/hMG/TDI cycles (16.6%; 95% CI: 2, 57%) (OR⫽1.5) (p⫽NS). CONCLUSION: Stimulation protocols employing CC, and/or hMG, in combination with TDI, do not achieve a significantly higher pregnancy rate over unstimulated cycles utilizing TDI alone. An unstimulated TDI cycle is therefore a reasonable first-line treatment approach for achieving pregnancy in advanced aged women lacking a male partner. Furthermore, in advanced reproductive aged women, TDI cycles result in pregnancy rates comparable to those seen in fertile couples of similar age. Supported by: None.
P-16 Poor oocyte retrieval ⴚ A manifestation of low ovarian reserve. J. S. Younis, A. Skournik, O. Radin, S. Haddad, S. Bar-Ami, M. Ben-Ami. Poriya Medical Center, Tiberias, Israel. OBJECTIVE: An ongoing debate is still in progress regarding the pathophysiology of the empty follicle syndrome (EFS). Nevertheless, to the best of our knowledge this syndrome has not yet been related to low ovarian reserve. Therefore, our study has been undertaken in order to gain insight into the EFS and to investigate whether it could be a manifestation of low ovarian reserve. DESIGN: A retrospective evaluation of all IVF cycles in a university affiliated reproductive medicine unit. MATERIALS AND METHODS: Four hundred thirty-nine consecutive IVF cycles, performed to 219 infertile patients, between Jauary 1998 and March 2002, were evaluated. Twenty-eight out of 439 cycles did not reach retrieval, due to poor ovarian response, and therefore were not included in the primary evaluation. All other 411 cycles were divided into 3 groups. Group I included cycles with complete absence of oocytes during retrieval (EFS). Group II included cycles that had below the 10th percentile of the expected number of oocytes retrieved. Group III included the controls. The standard long GnRH-agonist and hMG protocol was employed in all cycles. Oocyte retrieval was performed 34 –36 hours following hCG administration in all cycles. RESULTS: Seven cycles were in group I, 49 in group II and 355 in group III. In all 7 cycles of group I, measurable serum beta hCG levels were detected on the day of pick-up, between 120 –220 mIU/mL, negating a technical problem in hCG administration. The mean age of women in group I and group II were significantly higher than the controls corresponding to 36.4⫾5.5, 33.9⫾5.9 and 31.4⫾6.1 years, respectively. Moreover, day 3 serum FSH level was significantly higher in group I and group II as compared to controls, corresponding to 13.3⫾6.1, 9.4⫾4.4 and 6.5⫾2.5 mIU/mL, respectively. In addition, serum E2 level on hCG day were lower in groups I and II in contrast to group III, 680⫾471,1430⫾1073 and 1973⫾1210 pg/mL, respectively. As well, hMG requirement was significantly higher in groups I and II as compared to controls. The number of ⱖ14 mm follicles on hCG day were 5.0⫾3.6, 8.2⫾6.0 and 9.6⫾5.9, respectively. The number of oocytes were nil, 3.0⫾2.2 and 11.4⫾6.8, respectively. Clinical pregnancy rate was lower in group II as compared to controls corresponding to 10% and 28%, repectively. CONCLUSION: Infertile patients with complete absence of oocytes during retrieval (EFS), as well as those below the 10th percentile of the expecetd number of oocytes retrieved have clear manifestations of low ovarian reserve. It seems that this phenomenon is a gradual biological occurrence related to the same basic pathophysiology of ovarian ageing. Supported by: None
P-17 Should diagnostic laparascopy be performed in infertility work-up program in patients with unexplained infertility or male subfertility? S. Kursun, M. Akar, M. Simsek, M. Uner, O. Taskin. Akdeniz University School of Medicine, Antalya, Turkey.
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P-15 Therapeutic donor insemination (TDI) in advanced reproductive aged women: Impact of cycle type on success. S. Ghadir, A. Huang, E. Mor, A. H. Decherney, R. P. Buyalos, K. L. Durinzi. David Geffen School of Medicine at UCLA, Los Angeles, CA; Keck School of Medicine at USC, Los Angeles, CA; Kaiser Permanente Medical Center, Los Angeles, CA. OBJECTIVE: Currently, single women who seek fertility rely on sperm donation and TDI for conception. It is possible that with advancing reproductive age these women will benefit from the use of superovulation in combination with TDI to increase their overall pregancy success. To test this hypothesis we compared pregnancy rates following different superovulation regimens in single normo-ovulatory women ages 35– 43 years undergoing TDI. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Subjects included all consecutive women presenting between 1/1/96 and 12/31/01 at two large communitybased hospitals for TDI. Subjects were all single and without a male partner, older than 35 yrs, eumenorrheic, and with tubal patency confirmed by hysterosalpingography. Subjects began treatment with TDI alone, and were advanced to TDI plus superovulation (see below) if not pregnant. Superovulation consisted of clomiphene citrate (CC) 100 mg/day 3–7 of the cycle(CC⫹TDI), followed by either human menopausal gonadotropin (hMG) 150 IU/day as the starting dose (hMG⫹TDI) or a combination of CC 100 mg on cycle days 3–7 plus hMG 150 IU initiated on cycle day 8 (CC⫹hMG⫹TDI). TDI was performed 12–14 hours following timed ovulation, as determined by an ovulation prediction kit in unstimulated cycles (TDI only), or 34 –36 hours following hCG 10,000 IU in stimulated cycles. The main outcome variable was clinical pregnancy rate per cycle, stratified according to treatment type. Statistical analysis was by Student’s t test and chi-square test. RESULTS: Thirty-six women, mean age 39.1 ⫾ 2.4 yrs (range: 35 to 43 yrs), met entry criteria and underwent a total of 148 cycles of TDI; 72% had prior conceptions. Twenty-five cycles were unstimulated (TDI alone), 70 were CC⫹TDI, 47 were hMG⫹TDI, and 6 were CC⫹hMG⫹TDI. Mean patient ages were similar for TDI alone CC⫹TDI, hMG⫹TDI, and CC⫹hMG⫹TDI cycles (39.2 ⫾ 2.6 yrs, 38.5 ⫾ 2.1 yrs, 38.6 ⫾ 2.4 yrs, and
FERTILITY & STERILITY威
37.5 ⫾ 0.7 yrs, respectively) (p⫽NS). Overall, mean cycle day 3 FSH and estradiol levels were 8.3 ⫾ 4.8 mlU/mL and 47.8 ⫾ 21.6 pg/mL, respectively, while levels were similar among the 4 treatment groups (p⫽NS). The overall per cycle clinical pregnancy rate was 11.4% (95% CI: 7,18%). The overall delivery rate per cycle was 7.4%. The clinical pregnancy rate observed in cycles utilizing TDI only (11.5%; 95% CI: 3, 34%), was similar to the per cycle pregnancy rate observed in CC/TDI cycles (8.6%; 95% CI: 3, 18%) (OR⫽ 0.7), hMG/TDI cycles (14.9%; 95% CI: 7–28%) (OR⫽1.3), and CC/hMG/TDI cycles (16.6%; 95% CI: 2, 57%) (OR⫽1.5) (p⫽NS). CONCLUSION: Stimulation protocols employing CC, and/or hMG, in combination with TDI, do not achieve a significantly higher pregnancy rate over unstimulated cycles utilizing TDI alone. An unstimulated TDI cycle is therefore a reasonable first-line treatment approach for achieving pregnancy in advanced aged women lacking a male partner. Furthermore, in advanced reproductive aged women, TDI cycles result in pregnancy rates comparable to those seen in fertile couples of similar age. Supported by: None.
P-16 Poor oocyte retrieval ⴚ A manifestation of low ovarian reserve. J. S. Younis, A. Skournik, O. Radin, S. Haddad, S. Bar-Ami, M. Ben-Ami. Poriya Medical Center, Tiberias, Israel. OBJECTIVE: An ongoing debate is still in progress regarding the pathophysiology of the empty follicle syndrome (EFS). Nevertheless, to the best of our knowledge this syndrome has not yet been related to low ovarian reserve. Therefore, our study has been undertaken in order to gain insight into the EFS and to investigate whether it could be a manifestation of low ovarian reserve. DESIGN: A retrospective evaluation of all IVF cycles in a university affiliated reproductive medicine unit. MATERIALS AND METHODS: Four hundred thirty-nine consecutive IVF cycles, performed to 219 infertile patients, between Jauary 1998 and March 2002, were evaluated. Twenty-eight out of 439 cycles did not reach retrieval, due to poor ovarian response, and therefore were not included in the primary evaluation. All other 411 cycles were divided into 3 groups. Group I included cycles with complete absence of oocytes during retrieval (EFS). Group II included cycles that had below the 10th percentile of the expected number of oocytes retrieved. Group III included the controls. The standard long GnRH-agonist and hMG protocol was employed in all cycles. Oocyte retrieval was performed 34 –36 hours following hCG administration in all cycles. RESULTS: Seven cycles were in group I, 49 in group II and 355 in group III. In all 7 cycles of group I, measurable serum beta hCG levels were detected on the day of pick-up, between 120 –220 mIU/mL, negating a technical problem in hCG administration. The mean age of women in group I and group II were significantly higher than the controls corresponding to 36.4⫾5.5, 33.9⫾5.9 and 31.4⫾6.1 years, respectively. Moreover, day 3 serum FSH level was significantly higher in group I and group II as compared to controls, corresponding to 13.3⫾6.1, 9.4⫾4.4 and 6.5⫾2.5 mIU/mL, respectively. In addition, serum E2 level on hCG day were lower in groups I and II in contrast to group III, 680⫾471,1430⫾1073 and 1973⫾1210 pg/mL, respectively. As well, hMG requirement was significantly higher in groups I and II as compared to controls. The number of ⱖ14 mm follicles on hCG day were 5.0⫾3.6, 8.2⫾6.0 and 9.6⫾5.9, respectively. The number of oocytes were nil, 3.0⫾2.2 and 11.4⫾6.8, respectively. Clinical pregnancy rate was lower in group II as compared to controls corresponding to 10% and 28%, repectively. CONCLUSION: Infertile patients with complete absence of oocytes during retrieval (EFS), as well as those below the 10th percentile of the expecetd number of oocytes retrieved have clear manifestations of low ovarian reserve. It seems that this phenomenon is a gradual biological occurrence related to the same basic pathophysiology of ovarian ageing. Supported by: None
P-17 Should diagnostic laparascopy be performed in infertility work-up program in patients with unexplained infertility or male subfertility? S. Kursun, M. Akar, M. Simsek, M. Uner, O. Taskin. Akdeniz University School of Medicine, Antalya, Turkey.
S141