morphine doses (1–2 mg) could be taken by patient controlled analgesia (PCA) or by bolus, which was permitted at any time. Remedication with study medication occurred at 12 and 24 hours after the first dose. The amount of morphine consumed within 24 hours was analyzed in the set of patients who received study medication prior to first the morphine dose and within 30 minutes of the end of surgery (“per protocol” cohort), and in the intent to treat (ITT) cohorts, using analysis of covariance (with treatment and center as factors and baseline pain intensity as a covariate). Additional standard pain assessments such as Patient’s Global Evaluation of Study Medication were made. Results: In the set of patients where study medication was administrated within 30 minutes of the end of surgery and prior to administration of morphine, patients receiving parecoxib sodium 20 mg and 40 mg used 18% and 36% less total morphine (bolus plus PCA) than placebo-treated patients (p ⱕ 0.05). In contrast, the ITT cohort, including those who did not receive study drug prior to the first dose of morphine, did not exhibit significant differences in morphine consumption in the three study groups. Mean morphine consumption was 51.1 mg in the placebo group and 50.7 mg and 48.5 mg in the parecoxib sodium 20 mg and 40 mg groups. During the final Patient’s Global Evaluation of Study medication a greater proportion of the parecoxib sodium 20 mg and 40 mg groups (96% and 95%) rated their study medication as good or excellent compared to placebo (84%). Finally parecoxib sodium 20 mg or 40 mg administered in combination with morphine was well tolerated with no significant differences in adverse event rates. Conclusions: Parecoxib sodium demonstrates opioid sparing effects when administrated immediately after surgery and prior to post-operative morphine administration. These results are consistent with the opioid sparing properties of parecoxib sodium observed in other postoperative pain models. Supported by: Sponsored by Pharmacia Corporation.
WEDNESDAY, OCTOBER 24, 2001 ART: CLINICAL ART P-326 Factors affecting embryo transfer and subsequent pregnancy outcomes in in vitro fertilization. M. J. Heard, R. B. Lathi, J. E. Buster, P. Cisneros, P. Casson, S. A. Carson. Baylor Coll of Medicine, Houston, TX; Stanford Univ Sch of Medicine, San Francisco, CA; Univ of Vermont, Burlington, VT. Objective: The objective of this study is to evaluate the relationship of embryo transfer difficulty and uterine position to subsequent pregnancy outcomes with In Vitro Fertilization (IVF) Embryo Transfer (ET). Design: Retrospective analysis. Materials/Methods: A retrospective review of all IVF-ET cycles from 1996 –1998 at Baylor College of Medicine. Uterine position and trial transfer were recorded at the initial visit. All patients underwent a standard Lupron-Pergonal威 stimulation, oocyte retrieval, and ET. Subjective assessment of difficulty for each ET was recorded as one of 4 categories: none, minimal, moderate, or very difficult. A Wallace Catheter威 was used for all transfers. If the catheter did not pass easily, three techniques were used to facilitate transfer: a catheter sheath, a pipelle, or a cervical stitch to place traction on the cervix. If embryos were retained in the catheter, they were transferred again. Measures of transfer difficulty were recorded on the day of transfer. Final pregnancy outcome was correlated with transfer difficulty. Results: In 401 cycles analyzed, 239 (60%) were anteverted, 107 (27%) were retroverted, 51 (13%) were mid position and in 4 uterine position was not recorded. The latter two groups were excluded from analysis for uterine position. Women with anteverted and retroverted uteri were similar in age, parity, diagnosis, and number of embryos transferred. Pregnancy rates and “take home baby” rates were 42.3% and 35.1% for anteverted group and 33% and 26.8% in the retroverted group. The subjective difficulty, as recorded by the physician operator was none to minimal in 362 (90%) of patients and moderately to very difficult in 39 (10%). These groups were similar in age and number of embryos transferred. “Take home baby” rates were also similar in the two groups: 31.5% in the minimally difficult transfers and 25.6% in moderately to very difficult transfers. Cervical stitch placement, passage of a catheter, dilation with a pipelle or retained embryos were examined both separately and additively for effects on pregnancy rates. None of these factors, when examined separately, were found to be
FERTILITY & STERILITY威
significant predictors of pregnancy outcomes. These 4 factors combined to form a scoring system. Each factor, when present, added to 1 point to the patient’s score, with maximum score being 4. The pregnancy rates were 39.6%, 39.4%, 31.6% and 23.8% respectively for patients with transfer difficulty scores of 0,1,2, and 3. Only one patient had a score of 4; she did not conceive. Only maternal age greater than 35 and number of embryos transferred were found to be significant predictors of “take home baby” rates. Conclusions: Difficulty of embryo transfer did not have a signficiant impact on pregnancy outcome after IVF. Rather, maternal age and number of embryos transferred were significant predictors of live birth rates. Supported by: Baylor College of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility.
P-327 What happens to couples after assisted conception: Social and medical outcome after the end of treatment in couples who failed to conceive from treatment. D. J. Cahill, J. Meadowcroft, E. Corrigan. Univ of Bristol Ctr for Reproductive Medicine, Bristol, UK. Objective: We accept that IVF and assisted conception treatments are generally stressful. In addition, not everyone succeeds in achieving a pregnancy through our intervention. We wanted to know what happens to couples after they leave our centre. To determine the continuing likelihood of conception and the effect on their family life, couples who had previously undergone unsuccessful assisted conception treatment were sent a postal questionnaire to ascertain these details. Design: Postal questionnaire survey to all patients treated in a Private University IVF Centre more than three years previously (with follow-up by further questionnaire and telephone if necessary). Materials/Methods: 463 consecutive couples who had assisted conception treatment at our Centre at least three years before the survey were sent a structured questionnaire. Through this, information was obtained on whether further attempts were made to conceive with or without treatment elsewhere and the outcome, whether couples had adopted a child and whether the couple had separated, divorced or moved house since the end of treatment. The main outcome measures were: Proportion of women conceiving following further treatment elsewhere or without treatment; time to conception without treatment; pregnancy outcome in these women; significant changes in domestic circumstances (moved house/divorced/separated); whether the couple had adopted a child or children. Results: Of 463 couples surveyed, 121 were not contactable, presumably having moved. 149 of the remainder replied. Of the 149, 32% had adopted, 5% were divorced and in their replies, a further 2% said they had moved house. Of the 149 who replied, 34 had treatment, 114 did not. Of the 34 with further treatment, 14 conceived and all carried at least one baby to term. Of the 114 who had no further treatment, 48 conceived (after a median 7 months from cessation of treatment; range 1-84 months) and 41 carried at least one baby to term. Of those who conceived, 40% conceived within 6 months, 50% by a year, and 65% by 2 years. Allowing for the nonresponders, a minimum cumulative conception rate of 21% over 2 years was observed. Data relating these findings to the couples’ original diagnosis will be presented. Conclusions: The response rate was low, but the nature of the survey and the time since treatment may have influenced this. The rates of marital separation and divorce are probably falsely lowered by the poor response. The likelihood of conception after treatment was high, considering these are couples with prolonged infertility; this may reflect some pharmacological or physiological effect. After discontinuation of treatment, couples will still try elsewhere hoping for better (more successful) treatment. In addition, these data support the suggestion that many couples will ultimately conceive if they persist for long enough.
P-328 Presence of cervical mucus at embryo transfer and in vitro fertilization (IVF) outcome. A. P. Singh, C. A. Sattler, D. G. Hammitt. Mayo Clin Scottsdale, Scottsdale, AZ. Objective: Cervical mucus aspiration prior to embryo transfer (ET) has been recommended to optimize IVF outcomes. Potential concerns with
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cervical mucus present at time of ET include decreased transfer efficiency and increased incidence of retained embryos. However, the technique of cervical mucus aspiration may have adverse consequences. These include possible induced cervical bleeding, increased uterine contractility, or unintentional injection of aspiration fluid into the uterine cavity. The purpose of this study was to analyze the impact of cervical mucus on or in the ET catheter on IVF outcomes using standard ET techniques. Design: Retrospective cohort analysis. Materials/Methods: From 9/14/99 to 12/31/00 65 Fresh IVF transfers with non-donor eggs were performed. Controlled ovarian hyperstimulation involved standard protocols with either GnRHa down regulation followed by recombinant FSH, or GnRHa flare and recombinant FSH. Oocyte retrieval was performed 36 hours following hCG administration. Transfers were performed 3 days following retrieval. 47 transfers were with the Edward-Wallace (EW) catheter (72%) and 18 were with the Casmed catheter (28%). Transfer technique in all cases involved simple cleansing of cervical os with cotton tipped swabs dipped in buffered saline. Trial transfer was performed prior to actual transfer. Following actual transfer the ET catheter was evaluated by the embryologists for the presence of cervical mucus on or in the catheter. Results: 44 embryo transfers had no cervical mucus (CM) noted on ET catheter. 21 transfers had CM present. Clinical pregnancy rate per transfer in the CM group was 12/21 (57%) and in the no CM group was 20/44 (45%). This was not statistical significant (NS). Ongoing Pregnancy rate per transfer was 8/21 (38%) in the CM group and 16/44 (36%) in the no CM group. This was also NS. There was also NS difference between groups (CM versus no CM) in age (35.2 versus 35.9), number of embryos transferred (3.2 versus 2.8), or embryo grades (0.87 versus 0.86). There was one case with a retained embryo when mucus was present. No retained embryos were seen in any cases with no CM present. 5 transfers required more than one transfer attempt. There was NS association of CM presence with more than one transfer attempt. Finally there was NS difference in presence of mucus in EW verses Casmed transfer cycles. Conclusions: In this study, the presence of cervical mucus on or in the ET catheter at time of embryo transfer did not impact IVF outcome. Further studies are in progress to evaluate whether small versus significant amounts of cm at ET impact IVF outcomes. CM aspiration before ET may not improve IVF success rates and should be used with caution.
P-329 Comparison of two different long GnRH-␣ protocols in normal responding women undergoing IVF/ICSI. I. Aruh, F. Karaarslan, T. Pinar, D. Aslan, R. Keles, N. Demir. Irenbe Reproductive Medicine Ctr, Izmir, Turkey; SSK Izmir Maternity Hosp, Izmir, Turkey. Objective: Long protocols with GnRHa for IVF/ICSI cycles can be planned using different preparations. A single dose long acting GnRHa protocol is compared with a short acting daily GnRHa protocol in normal responding women undergoing IVF/ICSI. Design: Retrospective analysis of 63 consecutive cycles. Materials/Methods: From August 1998 to August 1999, all normal responding women undergoing IVF/ICSI in our center used a single dose long acting GnRHa preparation, triptorelin (Decapeptyl Depot, Ferring), in 38 cycles (Group A). After August 1999 we switched to a daily short acting GnRHa preparation, buserelin (Suprefact nasal, Hoechst), in similar cases assigned to use long protocol. Since we added the use of recFSH preparations and blastocyst transfers to our practice after May 2000, only the patients enrolled before this date using urinary FSH/HMG preparations and having day 3 embryo transfers (ET) were included in the study. In Group A, a single dose of 2.8 mg, which is 3⁄4 of a full syringe of Decapeptyl depot was administered IM on cycle day 1 after pretreatment with an oral contraceptive (OC) for 1 month. In Group B which consisted of 25 cycles, buserelin 0.9 mg/day as a nasal spray was started when the patient took the 15th pill of a 21 day OC pack and continued with 0.6 mg/day after 10 days, till the day of HCG. In Group A, two weeks after the depot GnRHa and in Group B on day 3 of the cycle, if a thin endometrial lining with no ovarian cyst was seen under ultrasound and E2 level was ⬍40 pg/ml, induction was started using a combination of urinary FSH (Metrodin HP, Serono) and HMG (Pergonal, Serono). Apart from the drugs used, all other clinical and laboratory protocols remained unchanged during the study period. P values were calculated by using Chi-square test for the rates and Student’s t test for comparing means.
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Abstracts
Results: Results are summarized in the table below.
Embryo transfer cycles Age (Mean ⫾ SD) Mean No. amps FSH/HMG Mean No. oocytes retrieved Mean No. of 2PN Mean Peak oestradiol (pg/ml) Mean no. embryos transferred Implantation rate Clinical pregnancy rate per transfer Livebirth rate per transfer
Group A
Group B
P
38 30.6 ⫾ 3.9 42.4 ⫾ 14.3 16.4 ⫾ 7.8 9.0 ⫾ 5.4 3416 ⫾ 1241 4.9 ⫾ 1.4 14.3% 36.8%
25 32.3 ⫾ 4.4 38.7 ⫾ 9.6 13.7 ⫾ 4.9 7.1 ⫾ 3.6 3109 ⫾ 1200 4.8 ⫾ 1.4 15.8% 40.0%
NS NS NS NS NS NS NS NS NS
28.9%
28.0%
NS
Conclusions: Although this retrospective study presents the data obtained from a limited number of patients, the two types of long protocols using a long acting (Decapeptyl Depot) or a short acting GnRHa preparation (Suprefact nasal) in normal responding women undergoing IVF/ICSI, yielded similar outcome comparing number of ampoules of FSH/HMG used, clinical pregnancy rates, implantation rates and livebirth rates. P-330 In vitro fertilization and embryo transfer for the treatment of couples with secondary infertility and a history of recurrent abortion. C. Alatas, S. Aksoy, R. Mercan, A. Mumcu, B. Urman. American Hosp of Istanbul, Istanbul, Turkey. Objective: Management of couples with recurrent abortion and secondary infertility using assisted reproductive techniques has been reported in the past. Although the initial study reported promising pregnancy rates and outcome the results were not substantiated. The aim of this study was to assess the role of IVF-ET in couples with three or more abortions with no demonstrable cause. Design: Prospective case series. Materials/Methods: A total of 21 couples with secondary infertility and a history of unexplained recurrent abortion were enrolled. All couples were evaluated with a hysterosalpingogram/hysteroscopy, measurement of anticardiolipin IgG, IgM and lupus anticoagulant, and male and female karyotype analyses. Standard infertility evaluation with semen analysis and documentation of ovulation was performed for all couples. Of the 21 couples, laparoscopy had been performed in 16. IVF-ET or ICSI was performed according to semen analysis of the male. All women were down regulated with a luteal start GnRH analogue and stimulated with pure or recombinant FSH. Up to 4 embryos were replaced depending on embryo quality and female age. Preimplantation genetic diagnosis was not carried out due to the unavailability of the technique at the time of the study. Results: Of the 21 couples, 5 had mild-moderate male factor, 6 had endometriosis, and 3 had anovulation. Women with endometriosis had their lesions fulgurated during surgery. Mean female age was 33.5 years (26 – 44) and mean duration of infertility was 4.5 years (1–11). Mean number of previous abortions was 3.9 (3–9). A total of 25 cycles of IVF/ICSI was performed. A mean of 11.1 oocytes (3–26) were retrieved and 2.8 (1– 4) embryos were transferred. One cycle was cancelled due to empty follicles. Clinical pregnancy per initiated cycle was 32% (8/25). Of the 8 pregnancies 2 delivered (1 singleton, 1 twin) and 5 ended in first trimester miscarriages. One twin pregnancy was terminated at 22 weeks due to severe preeclampsia. Take home baby rate was 8% (2/25) per cycle and 8.3% (2/24) per embryo transfer. At the same time period, clinical pregnancy rate per embryo transfer in our institution was 41% for all age groups included. Conclusions: Etiology of recurrent abortion is most probably multifactorial and complex. In couples with a history of recurrent abortion and secondary infertility, IVF/ICSI appears to yield very low delivery rates with most of the pregnancies achieved ending in spontaneous abortions. Preimplantation genetic diagnosis appears to be the approach of choice in these couples. P-331 Progesterone affects the cervix prior to embryo transfer. D. N. Senciboy, K. L. Sharpe-Timms. Univ of Missouri-Columbia, Columbia, MO.
Vol. 76, No. 3, Suppl. 1, September 2001