Therapeutic donor insemination (TDI) in advanced reproductive aged women: Impact of cycle type on success

Abstract

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. Retrospective cohort study. Subjects included all consecutive women presenting between 1/1/96 and 12/31/01 at two large community-based 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. 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 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). 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.